NOTES FROM LANGMAN’S MEDICAL EMBRYOLOGY
father or the mother is expressed
PART 1 (page 1 to 140)
GENE TRANSCRIPTION
 Genes are contained in a chromatin
o Chromatin = a complex of DNA and proteins
(histones)
o Basic unit of structure = nucleosome
 Each nucleosome is made up of:
o an octamer of histone proteins
o 140 base pairs of DNA
o Joined together by linker DNA
o Keep DNA tightly coiled
 HETEROCHROMATIN – chromatin that is inactive and
coiled
o Cannot be transcribed
 EUCHROMATIN – chromatin that is uncoiled
Gene Parts
 Contain exons – contain DNA sequences that can be
translated into proteins)
 Contain introns (found in between exons; cannot be
translated into proteins)
 Promoter region – this is where RNA polymerase binds
for the start of transcription
 Usually contains the sequence TATA (TATA box)
 5’
 Transcription initiation site
 Translation initiation site – to designate the first amino
acid in the protein
 Translation termination codon
 3’ Poly A addition site – untranslated; has a sequence that
assists with stabilizing the mRNA
o allows mRNA to exit the nucleus
o allows mRNA to be translated into protein
 Transcription termination site
Gene Transcription
 DNA is transcribed from the 5’ to the 3’ end
 Transcription factors (protein complex) are needed so that
RNA polymerase can bind to the TATA box in the
promoter region
o Have a DNA-binding domain – specific to a
region of DNA
o Have a transactivating domain – binds to a
promoter or an enhancer; activates or inhibits the
gene
o Activate gene expression – causes DNA
nucleosome complex to unwind
 Enhancers – regulatory parts of DNA
o Activate utilization of promoters to control
efficiency and rate of transcription from the
promoter
o Bind transcription factors through the
transcription factor’s transactivating domain
o Silencers – enhancers that inhibit transcription
DNA Methylation Represses Transcription
 DNA methylation of cytosine bases in the promoter
regions represses gene transcription
 Genes in different types of cells (Ex. muscle cells make
muscle proteins but not blood proteins)
 Genomic imprinting – only a gene inherited from the
OTHER REGULATORS OF GENE EXPRESSION
 Nuclear RNA (nRNA) – initial transcript of a gene
o Sometimes called premessenger RNA
o Longer than mRNA
o Contains introns that are removed (spliced out)
 Alternative spicing – forms different proteins from the
same gene
o Spliceosomes – complexes that recognize specific
splice sites
 Post-translational modifications
INDUCTION AND ORGAN FORMATION
 INDUCTION – one group of cells or tissues causes
another set of cells or tissues to change their fate; how
organs form
o Inducer – produces signal; initiates induction
o Responder – to signal
o Competence – capacity to respond to a signal
 requires activation of the responding
tissue by a competence factor
 Epithelial-mesenchymal interactions
 Crosstalk – between tissues or cells; needed for
differentiation to continue
CELL SIGNALING
 Needed for induction, competency to respond, and
crosstalk
 Paracrine interactions – involves diffusible proteins
o Paracrine factors
o Growth and differentiation factors
 Juxtacrine interactions – no diffusible proteins involved
SIGNAL TRANSDUCTION PATHWAYS
Paracrine Signaling
 Paracrine factors act by signal transduction pathways
o ST Pathways – include a signaling molecule
(ligand) and a receptor
o Paracrine factors are important during
development
 Receptor
o Has a ligand-binding region
o Transmembrane domain
o Cytoplasmic domain
 When a ligand binds its receptor, there’s a change that
activates the cytoplasmic domain. This is to confer
enzymatic activity to the receptor.
o Kinase
o Phosphorylation
 Phosphorylation of proteins activates a transcription factor.
o Transcription factor activates or inhibits gene
expression.
Juxtacrine Signaling
 Mediated through signal transduction pathways
 Does not involve diffusible factors
 Occurs in three ways:
o A protein on one cell interacts with a receptor on
an adjacent cell
 o Ligands in the extracellular matrix interact with o Limbs
their receptors on neighboring cells. o Smooth muscle pattern
o Direct transmission of signals from one cell to o Heart
another by gap junctions o Gut
 Important in tightly connected cells o Pharynx
o Lungs
Note: Ligands = GDFs o Pancreas
o Kidneys
Paracrine Signaling Factors - Regulate development and o Bladder
differentiation of organ systems
o Hair follicle
 Four families:
o Teeth
1. Fibroblast Growth Factor (FGF)
o Thymocytes
2. WNT
3. Hedgehog o Inner ear
4. Transforming Growth Factor-Beta (TGF-Beta) o Eyes
o Taste buds
Fibroblast Growth Factors:  Sonic signaling –
 Stimulate the growth of fibroblasts in culture o SHH protein binds to protein receptor Patched.
 Can produce hundreds of protein isoforms by altering their When this happens, Patched stops inhibiting Smo,
RNA splicing or their initiation codons and Smo is activated.
 Important for angiogenesis, axon growth, and mesoderm  Patched inhibits the protein Smoothened
differentiation (normally)
 Activate FGFRs (fibroblast growth factor receptors) o When Smo is activated, it upregulates the activity
 Responsible for specific developmental events (ex. devt. of of GLI.
brain parts)  GLI – transcription factors that control
target gene expression
Hedgehog Proteins o SHH is cleaved after translation and cholesterol is
 Code for a pattern of bristles on the leg that look like a added to it. This adding of cholesterol is what
hedgehog links the SHH to the plasma membrane.
 Sonic hedgehog – involved in many developmental events  Cholesterol is added to its N-terminal
domain
WNT Proteins o Dispatched (transmbembrane protein) releases
 Involved in regulating limb patterning, midbrain SHH from the plasma membrane
development, and somite and urogenital differentiation
The Planar Cell Polarity: Convergent Extension Pathway
TGF-Beta Superfamily  The PCP regulates the process of convergent extension
 Important for forming extracellular matrix, epithelial  Convergent extension is a process in which a tissue
branching, and bone formation becomes longer and narrower.
 Regulates cell division, cell death (apoptosis), and cell o Ex. Elongation of neural plate to form neural
migration groove
 PCP – is the reorganization of cells and cell sheets in the
Other Paracrine Signaling Molecules plane of a tissue (like what happens during convergent
 Neurotransmitters – provide important signals for extension)
embryological development  WNT pathway - Main PCP signaling pathway
o Serotonin, GABA, epinephrine, norepinephrine o Includes Frizzled, Celsr, and Vangl
o Act as ligands and bind to receptors like proteins
do The Notch Pathway
o Serotonin – cell proliferation and migration,  Notch receptors bind to ligands of the DSL (Delta-Serrate-
establishing laterality, gastrulation, heart LAG-2)
development  No second messengers involved here
o Norepinephrine – apoptosis  Function: binding to a notch receptor results in cleavage of
Notch protein
KEY SIGNALING PATHWAYS FOR DEVELOPMENT  Notch protein then goes inside the nucleus and binds onto
a DNA-binding protein. This stops the normal inhibiting of
Sonic Hedgehog: Master Morphogen/Gene for Embryogenesis transcription of Notch proteins.
 Morphogen – a molecule that establishes concentration  The Notch signaling is involved in:
gradients and instructs cells on how to become different o Cell proliferation
tissues and organs o Apoptosis
 SHH (a protein) – involved in devt. of: o Epithelial to mesenchymal transitions
o Vasculature  Notch is important in:
o Axis formation o Neuronal differentiation
o Midline o Blood vessel formation (angiogenesis)
o Cerebellum o Somite segmentation
o Neural patterning o Pancreatic beta-cell development
 o B- and T- cell differentiation
o Devt. of inner ear hair cells
o Septation of heart’s outflow tract
 Alagille syndrome – cardiac outflow tract defects and
other abnormalities; caused by NOTCH mutation
Note: Mesenchyme is a tissue found in organisms during
development. It’s derived from the mesoderm.
CHAPTER 2—GAMETOGENESIS: CONVERSION OF GERM
CELLS INTO MALE AND FEMALE GAMETES
PRIMORDIAL GERM CELLS
 Fertilization is the process by which sperm (male gamete)
and oocyte (female gamete) unite to make a zygote.
 Primordial germ cells – where gametes come from
 During the second week of development, PGCs are formed
in the epiblast
 During the fourth week, PGCs start migrating to the yolk
sac to the developing gonads.
 Dufring the fifth week, PGCs finally arrive at the gonads.
 Gametogenesis – to prepare for fertilization, germ cells
have to go through this
o Includes meiosis
o Includes cytodifferentiation
CLINICAL CORRELATES
 Terratomas – tumors of disputed origin that often contain
a variety of tissues (ex. bone, hair, muscle, gut, etc)
 May arise from PGCs or from epiblast cells (Both of these
are pluripotent cells)
 Tissues withn the tumors include derivatives from all three
germ layers
CHROMOSOME THEORY OF INHERITANCE
 Linked genes – genes on the same chromosome that are
inherited together
 Cells from all 46 chromosomes = diploid (mitosis)
 Cells from 23 chromosomes = haploid (meisosis)
 In body cells (somatic), there are 23 homologous pairs of
chromosomes. SO, somatic cells are haploid cells, because
23 x 2 = 46 chromosomes.
o Diploids = 46 chromosomes = somatic cells =
mitosis
o Haploids = 23 chromosomes = sex cells = meiosis
 Diploids:
o 22 pairs of autosomes (matching chromosomes)
o 1 pair of sex chromosomes
o for a total of 23 homologous pairs or 46
chromosomes
 Gametes:
o 1 chromosome of a pair = from oocyte (maternal
gamete), 1 chromosome of a pair = from sperm
(paternal gamete)
o Each gamete is a haploid = 23 chromosomes only
MITOSIS
 Each daughter cell gets 46 chromosomes. When a cell
divides, the daughter cell still gets the same amount of
chromosomes.
 Before mitosis, a cell will go through DNA replication.
Each chromosome replicates its DNA. In this phase,
chromosomes are super long and are spread out.
 PROPHASE
o Chromosomes start to condense, shorten, and
thicken.
o Chromosomes join together to form chromatids.
Chromatids are joined together by centromeres.
o However, the chromatids are not distinguishable
yet here. Note: chromatid = one tube from the
chromosome
 PROMETAPHASE
o Chromatids are distinguishable.
 METAPHASE
o Chromosomes line up in the equatorial plane.
o Centrioles have microtubules which attach to the
centromeres of the chromosomes. – this
microtubule set-up is called the mitotic spindle
 ANAPHASE
o Centromere of each chromosome divides.
o The chromatids go to the opposite ends of the
spindle.
o Note: Individual chromatids are also referred to as
chromosomes.
 TELOPHASE
o Chromosomes uncoil and lengthen.
o Nuclear envelope forms again.
o Cytoplasm divides (cytokinesis).
 ENDING:
o Each daughter cell gets the same number of
chromosomes as the mother cell.
MEIOSIS
 Happens in the GERM CELLS = spermatocytes and
primary oocytes
 Purpose: to make male and female gametes (sperm and
oocyte)
 Involves two cell divisions
o Why? Because one cell division = 46
chromosomes. 2 cell divisions = 23
chromosomes.
o To REDUCE the number of chromosomes to
haploid
 Before meiosis, the GERM CELLS (M and F), replicate
their DNA.
 Synapsis – two homologous chromosomes pair with each
other in a tetrad structure
o Happens during Prophase 1
 Involves homologous chromosome pairing (SYNAPSIS)
and CROSSOVER
Crossovers
 Happen in Meiosis 1
 This is the interchange of chromatid segments between
PAIRED homologous chromosomes
 Allows recombination of genes between homologous
chromosomes
 Segments of chromatids break and are exchanged as the
homologous chromosomes separate
 Chiasma (X-like structure) formation during separation
 Enhances genetic variability
Polar Bodies
 In meiosis, ONE (1) primary oocyte makes four daughter
cells.
o Each daughter cell has 22 autosomes and 1 X
chromosome.
 o Only one of these will develop into a mature f. Incidence increases with age
oocyte. i. 1 in 2000 – under 25
o The other three are the polar bodies and they will ii. 1 in 300 - 35
degenerate. iii. 1 in 100 – 40
 In meiosis, ONE (1) primary spermatocyte makes four g. 4% unbalanced translocation
daughter cells. h. 1% mosaicism from mitotic nondisjunction
o Two have 22 autosomes + 1 X chromosome.
o Two have 22 autosomes + 1 Y chromosome. 2. TRISOMY 18
o All four develop into mature spermatids. a. Intellectual disability
b. Congenital heart defects
c. Low-set ears
Meiosis
d. Flexion of fingers and hands
Primary oocyte Primary spermatocyte
e. Micrognathia
Four daughter cells Four daughter cells
f. Syndactyly
Each has 22 + X chromosome Two have 22 + X chromosome g. Skeletal system malformation
Two have 22 + Y chromosome h. 1 in 5,000
Only one will become a All become mature gametes i. High death rate – 1 year or less
mature gamete (oocyte) (spermatids)
Polar bodies will degenerate 3. TRISOMY 13
a. Intellectual disability
CLINICAL CORRELATES b. Holoprosencephaly
c. Congenital heart defects
Birth Defects and Spontaneous Abortions: Chromosomal d. Deafness
Abnormalities e. Cleft lip palate
 Chromosomal abnormalities can be: f. Eye defects
o NUMERICAL g. 1 in 20,000
o STRUCTURAL h. High death rate – 1 year or less
 50% of spontaneous abortions have CAs
 10% of birth defects are from CAs 4. Klinefelter Syndrome – 47 chromosomes; XXY
 8% of birth defects are from gene mutations a. Sterility
 A normal somatic cell is 2n (diploid). b. Testicular atrophy
c. Gynecomastia (man boobs)
NUMERICAL ABNORMALITIES d. Barr body
 EUPLOID – any exact multiple of n; there is a change in
the number of chromosomes by set 5. Turner Syndrome – 45, X
o Ex. 1 extra chromosome per set a. Only monosomy that allows life
o Triploidy – 3n b. Female in appearance
o Tetraploidy – 4n c. No ovaries (gonadal dysgenesis)
o Pentaploidy – 5n d. Short stature
e. Webbed neck
 ANEUPLOID – change in chromosome number by 1
f. Lymphedema (swelling of legs or arms)
(usually 1 extra or 1 missing)
g. Skeletal deformities
o 2n + 1 = Trisomy = 47 chromosomes
h. Widely spaced nipples
o 2n – 1 = Monosomy = 45 chromosomes i. Nondisjunction in male gamete
o 2n – 2 = Nulisomy
o A result of nondisjunction – failure of chromatids 6. Triple X Syndrome – 47, XXX
to separate during 1st or 2nd meiotic division a. Often undiagnosed
 Mitotic nondisjunction – occurs during mitosis; produces b. Speech problem
mosaicism c. Self-esteem problem
o Mosaicism – some cells have abnormal numbers, d. Two sex chromatin bodies in cells
while others don’t
 Translocation – when pieces of one chromosome attach to STRUCTURAL ABNORMALITIES - caused by chromosome
another breakage
o Balanced – no genetic material is lost; normal 1. Cri Du Chat – partial deletion in Chromosome 5
person a. Cat-like cry
o Unbalanced – part of one chromosome is lost b. Small head (microcephaly)
c. Intellectual disability
NUMERICAL ABNORMALITIES d. Congenital Heart Disease
1. DOWN SYNDROME (TRISOMY 21) 2. Angelman Syndrome – microdeletion on maternal
a. Extra copy of Chromosome 21 chromosome
b. Flat, broad face; protruding tongue a. Intellectual disability
c. Intellectual disability b. No speech
d. Broad hand with a simian crease c. Poor motor devt.
e. Caused by meiotic nondisjunction (most of the time) d. Laughter
i. During oocyte formation 3. Prader-Willi Syndrome – microdeletion on paternal
chromosome
 a. Hypotonia  Meiosis II is only completed if the oocyte is fertilized—
b. Obesity if not, then the cell degenerates 24 hours after
c. Intellectual disability ovulation.
d. Hypogonadism
e. Testes that don’t drop into place (undescended SPERMATOGENESIS – all the events by which spermatogonia
testes) are transformed into spermatozoa
4. Fragile X Syndrome  PGCs stay dormant until puberty
a. Intellectual disability  PGCs differentiate into spermatogonia at puberty.
b. Large ears  Primary spermatocytes – undergo two successive meiotic
c. Prominent jaw divisions  to produce 4 spermatids
d. Large testes  Spermatids go through spermiogenesis (a series of
changes)
GENE MUTATIONS o Acrosome formed
 Single gene mutation – one gene is affected only o Nucleus condensed
 Dominant mutation o Neck, middle, tail formed
 Recessive mutation o Cytoplasm (most) shed
 Inborn errors of metabolism  A spermatogonium takes 74 days to become a mature
spermatozoon
MORPHOLOGICAL CHANGES DURING MATURATION OF
THE GAMETES CHAPTER 3—FIRST WEEK OF DEVELOPMENT:
 Oogenesis – process whereby oogonia differentiate into OVULATION TO IMPLANTATION
mature oocytes; process by which the female gametes are
created OVARIAN CYCLE
 With each ovarian cycle, a lot of primary follicles start
1) Maturation of oocytes begins before birth (so, formation of growing, but only one becomes fully mature.
primary oocytes begins before birth):
 Thus, only one oocyte is released at ovulation.
 Once a primordial germ cell (PGC) gets to the ovary of a
 During ovulation, the oocyte is in METAPHASE of
female, it differentiates into oogonia.
Meiosis II.
o PGC undergoes mitotic division  Oogonium
o Surrounded by zona pellucida and granulosa cells
 Oogonia undergo mitotic division (series of them) 
 What carries the oocyte into the uterine tube is the
primary oocytes in prophase
sweeping action of the tubal fimbriae.
 Each primary oocyte is surrounded by primordial follicle.
FERTILIZATION
Note: Oogonia = immature female sex cell; Primary oocyte =
 Before spermatozoa can fertilize the oocyte, they must go
mature female sex cell
through a process:
 All of a female’s oogonia will be created while she is still 1. Capacitation
a fetus. The surviving oogonia will enter meiosis 1 and a. A glycoprotein coat and seminal plasma
become primary oocytes. proteins are removed from the sperm head
 After primary oocytes replicate their DNA, they stay in 2. Acrosome Reaction
prophase 1 of meiosis near birth. They stay in prophase a. Acrosin- and trypsin-like substances are
1 until the menstruation cycle begins 10-13 years after released
birth. b. Acrosin- and trypsin-like substances
 Then, for 30-45 years, every month, primary oocytes penetrate the zona pellucida
resume meiosis where they left off and complete Meiosis
1.  The sperm (spermatozoon) MUST penetrate:
1. Corona Radiata
2) Maturation of oocytes continues at puberty 2. Zona Pellucida
 Diplotene Stage – a resting stage during prophase; oocytes 3. Oocyte Cell Membrane
stay here until puberty
 Oocyte maturation inhibitor  As soon as the spermatocyte has entered the oocyte:
 600k-800k primary oocytes at birth 1. The oocyte finishes Meiosis II. It forms the FEMALE
 Antral stage – vesicular/antral follicle PRONUCLEUS.
 Mature vesicular stage – mature vesicular (graafian) 2. The ZONA PELLUCIDA becomes impenetrable to
follicle other spermatozoa.
o Theca interna – secretes steroids, rich in blood 3. The sperm’s head separates from the tail and swells. It
vessels forms the MALE PRONUCLEUS.
o Theca externa – merges with ovary’s CT
 In every ovarian cycle, only one follicle reaches full  The MALE AND FEMALE PRONUCLEI replicate their
maturity. The others become atretic. DNA.
 Luteinizing hormone - induces preovulatory growth phase  Afterwards, paternal and maternal chromosomes mingle
 Meiosis I completes and forms 2 daughter cells – one is a and split longitudinally.
secondary oocyte, the other is a polar body  They then go through mitotic division, giving rise to the
TWO-CELL STAGE.
  Results of Fertilization: a. Cortical and Zona Reactions
1. Diploid number of chromosomes is restored (half from b. Resumption of the 2nd Meiotic Division
mom and half from dad) c. Metabolic Activation of the Egg
2. Chromosomal sex is determined 4. What are the primary causes of infertility in men and women?
3. Cleavage is initiated a. Male – not enough sperm; poor motility
b. Female – occluded uterine tubes; hostile cervical
CLINICAL CORRELATES mucus; immunity to spermatozoa; absence of
 Infertility – a problem for 15% to 30% of couples ovulation
 Assisted Reproductive Technology (ART) – solution to
infertility CHAPTER 4—SECOND WEEK OF DEVELOPMENT:
 In Vitro Fertilization (IVF) – involves fertilizing eggs in BILAMINAR GERM DISC
a culture and then putting them in the uterus at the 8 th-cell
stage Day 8
 Intracytoplasmic Sperm Injection (ICSI) – a single  At the start of the second week, the blastocyst is partially
sperm is injected into an egg’s cytoplasm embedded in the endometrial stroma.
 Cons:  The trophoblast differentiates into:
o Higher risk for birth defects, prematurity, low o Cytotrophoblast - an inner, actively reproducing
birth weight, and multiple births layer
o Syncytiotrophoblast – an outer layer, erodes
maternal tissues
CLEAVAGE
 A series of mitotic divisions that results in an increase in
blastomeres. Day 9
o With each mitotic division, the blastomeres get  Lacunae develop in the syncytiotrophoblast (outer layer)
smaller.
 After three mitotic divisions, blastomeres undergo Days 11 and 12
compaction. They become a tightly grouped ball of cells  By this time, the blastocyst is completely embedded in the
with inner and outer layers. endomaterial stroma.
 Maternal sinusinoids are eroded by the
BLASTOCYST FORMATION syncytiotrophoblast.
 Compacted blastomeres divide to form a 16-cell morula.  Maternal blood enters the lacunar network.
 The morula enters the uterus on the third or fourth day
after fertilization. During this time, a cavity starts to Day 13
appear, and the blastocyst forms.  By this time, a primitive uteroplacental circulation begins.
 Inner cell mass – will develop into the embryo proper  The cytotrophoblast, meanwhile, forms primary villi
 Outer cell mass - will form the trophoblast (columns) that penetrate into the syncytium.
 Inner cell mass (embryoblast) differentiates into:
UTERUS AT TIME OF IMPLANTATION o Epiblast
 During this time, the uterus is in a secretory phase. o Hypoblast
o Uterine glands and arteries become coiled. o Together they form a bilaminar disc
 The blastocyst implants in the endometrium along the  Epiblast cells – give rise to amnioblasts
anterior or posterior wall.  Hypoblast cells – surround the primitive yolk sac
 If fertilization doesn’t happen, then the menstrual phase  By the end of 2nd week, extraembryonic mesoderm fills the
begins. space between the trophoblast and the amnion and
 Three layers in the endometrium: exocoelomic membrane.
o Compact layer – sheds during menstruation o The extraembronic coelom/chorionic cavity forms
o Spongy layer – sheds during menstruation when vacuoles develop in this tissue.
o Basal layer – the only part that is retained;  Extraembryonic somatic mesoderm – extraembryonic
regenerates other layers during the next cycle mesoderm lining the cytotrophoblast and amnion
 Extraembryonic splanchnic mesoderm – lining
1. What is corpus luteum? Role and origin? surrounding the yolk sac
a. A corpus luteum is a mass of cells that forms in an
ovary. The 2nd week of development is known as the week of 2’s:
b. It forms from the empty follicle left behind after 1. Trophoblast differentiates into two layers:
ovulation. a. Cytotrophoblast
c. It is responsible for producing progesterone during b. Synctiotrophoblast
early pregnancy. It is also involved in ovulation and 2. The embryoblast forms two layers:
regulation of menstrual cycle. a. Epiblast
2. What are the three phases of fertilization? b. Hypoblast
a. PHASE 1: Penetration of the corona radiate 3. The extraembryonic mesoderm splits into two layers:
b. PHASE 2: Penetration of the zona pellucida a. Somatic layer
c. PHASE 3: Fusion of the oocyte and sperm cell b. Splanchnic Layer
membranes 4. Two cavities form:
3. What actions occur during Phase 3 (fusion of the membranes)? a. Amniotic cavity
 b. Yolk sac cavity
CLINICAL CORRELATES
 Implantation happens at the end of first week.
 Trophoblast cells invade the epithelium and endometrial
stroma with the help of proteolytic enzymes.
 Implantation can happen outside the uterus (ectopic
pregnancies)
CHAPTER 5: THIRD WEEK OF DEVELOPMENT-
TRIMALINAR GERM DISC
GASTRULATION: FORMATION OF EMBRYONIC
MESODERM AND ENDODERM
 The major event that happens during the 3rd week
 It begins with a primitive streak appearance.
o At the cephalic end there is a primitive node.
 In the part with the node and streak, epiblast cells move
inward to form new cell layers:
o Endoderm
o Mesoderm
 Cells that don’t move through the streak but stay in the
epiblast form:
o Ectoderm
 So, EPIBLAST cells give rise to all three germ layers
(Endoderm, Mesoderm, Ectoderm):
o These form all of the tissues and organs
FORMATION OF THE NOTOCHORD
 Prenotochordal cells move forward until they reach the
prechordal plate.
 They intercalate in the endoderm as the notochordal
plate.
 After more development, the plate detaches from the
endoderm – and the NOTOCHORD is formed.
 The notochord forms a midline axis, which will serve as
the basis of the axial skeleton.
 Cephalic and caudal ends of the embryo are established
before the primitive streak is formed.
ESTABLISHMENT OF THE BODY AXES
 Cells in the hypoblast (endoderm) at the cephalic end form
the AVE (anterior visceral endoderm)
o The AVE– expresses head-forming genes (OTX2,
LIM1, HESX1)
 NODAL – involved in initiating and maintaining the
integrity of the node and streak
 With FGF present, BMP4 ventralizes mesoderm during
gastrulation so that it forms intermediate and lateral plate
mesoderm.
 Chordin, noggin, and follistatin antagonize BMP4 activity.
They dorsalize mesoderm to form the notochord and
somitomeres in the head region.
FATE MAP ESTABLISHED DURING GASTRULATION
 Epiblast cells moving through the node and streak are
predetermined by their position to become specific types
of mesoderm and endoderm.
GROWTH OF THE EMBRYONIC DISC
 By the end of the third week, three basic germ layers
(ectoderm, mesoderm, and endoderm) are established in
the head region.
 This process continues to produce germ layers for more
caudal areas of the embryo until the end of the 4th week.
 Tissue and organ differentiation has begun.
o It happens in a cephalocaudal direction.
o Gastrulation continues.
FURTHER DEVELOPMENT OF THE TROPHOBLAST
 Primary villi get a mesenchymal core in which small
capillaries arise.
 When these villous capillaries make contact with
capillaries in the chorionic plate and connecting stalk:
o The villous system is ready to supply the embryo
with its nutrients and oxygen.
CHAPTER 6—THIRD TO EIGHTH WEEKS: THE EMBRYONIC
PERIOD
 The embryonic period (3rd to 8th weeks) is the period
during which each of the 3 germ layers gives rise to its
own tissues and organ systems.
 Because organs are formed, major features of body form
are established.
DERIVATIVES OF THE ECTODERMAL GERM LAYER
 This germ layer rise to the organs and structures that
maintain contact with the outside world:
1. CNS
2. PNS
3. Sensory epithelium of EAR, NOSE, and EYE
4. Skin (including hair and nails)
5. Pituitary, Mammary, and Sweat Glands
6. Enamel of the teeth
 Induction of the neural plate is regulated by the
inactivation of BMP4 (a growth factor).
o Cranial region – inactivation is caused by Noggin,
Chordin, and Follistatin
o Hindbrain and Spinal Cord region – inactivation
is caused by WNT3a and FGF
DERIVATIVES OF THE MESODERMAL GERM LAYER
 Paraxial Mesoderm
 Intermediate Mesoderm
 Lateral Plate Mesoderm
 Paraxial mesoderm forms somitomeres
 Somitomeres give rise to mesenchyme of the head, which
is organized into somites.
 Somites give rise to:
o Myotome – muscle tissue
 Epimere
 Hypomere
o Sclerotome – cartilage and bone
o Dermatome – dermis
 Once SHH is secreted by the notochord and floor plate of
neural tube – it induces the sclerotome.
DERIVATIVES OF THE ENDODERMAL GERM LAYER
 Epithelial lining of the:
o GI Tract
o Respiratory Tract
o Urinary Bladder
o Tympanic Cavity
o Auditory Tube
 Parenchyma of the:
o Thyroid
o Parathyroids
 o Liver
o Pancreas
PATTERNING OF THE ANTEROPOSTERIOR AXIS:
REGULATION BY HOMEOBOX GENES
 Four clusters: HOXA, HOXB, HOXC, HOXD—on four
chromosomes
 Genes at the 3’ end – control development of cranial
structures
 Genes at the 5’ end – control development of posterior
structures
 Hindbrain and embryonic axis patterning is controlled
EXTERNAL APPEARANCE DURING THE SECOND MONTH
 Embryonic disc begins to get longer and to form head and
tail regions. This causes the embryo to curve into the fetal
position.
 The embryo also forms two lateral body wall folds that
grow ventrally and close the ventral body wall.
o This causes the amnion to be pulled ventrally –
and the embryo to lie within the amniotic cavity.
 Connection with the yolk sac and placenta is maintained
through:
o Vitelline duct
o Umbilical cord
CHAPTER 7: THE GUT TUBE AND THE BODY CAVITIES
A TUBE ON TOP OF A TUBE
 At the end of the third week, the neural tube is elevating
and closing dorsally while the gut tube is rolling and
closing ventrally to create a “tube on top of a tube”.
 Mesoderm holds the tubes together.
 The lateral plate mesoderm splits to form:
o Visceral (splanchnic) layer
o Parietal (somatic) layer
o These form the lateral body wall folds
 Primitive body cavity – space between the visceral and
parietal layers
 Failure of the ventral body wall to close results in --
Ventral Body Wall Defects:
o Ectopia Cordis
o Gastroschisis
o Exstrophy of the Bladder and Cloaca
FORMATION OF THE BODY CAVITY
SEROUS MEMBRANES
 Parietal mesoderm – forms parietal layer of serous
membranes (which line walls of):
o Peritoneal Cavity
o Pleural Cavity
o Pericardial Cavity
 Visceral Layer – forms visceral layer of serous
membranes
o Covers the lungs, heart, and abdominal organs
 Peritoneum – parietal and visceral layers in the abdomen
 Mesenteries – double layers of peritoneum; provide a path
for vessels, nerves, and lymphatics to the organs
o Dorsal Mesentery – suspends the gut tube from
the dorsal body wall
o Ventral Mesentery – exists only in part of the
esophagus, the stomach, and the upper part of the
duodenum
DIAPHRAGM AND THORACIC CAVITY
 Diaphragm – divides the body cavity into:
o Thoracic Cavity
o Peritoneal Cavity
 Thoracic Cavity is divided into (by the pleuropericardial
membranes):
o Pericardial Cavity
o Pleural Cavities (2)
FORMATION OF THE DIAPHRAGM
 Diaphragm - develops from four components:
1. Septum Transversum (Central Tendon)
2. Pleuroperitoneal Membranes
3. Dorsal Mesentery of the Esophagus
4. Muscular Components from Somites at C3-C5
a. C3, C4, and C5 keep the diaphragm alive
CHAPTER 8—THIRD MONTH TO BIRTH: THE FETUS AND
PLACENTA
DEVELOPMENT OF THE FETUS
 Extends from 9th week of gestation until birth
 Characterized by rapid growth of the body and maturation
of organ systems
 3rd, 4th, and 5th months – 5cm of growth per month
 last 2 months – 700 g of weight gain per month
 6 to 9 lb at birth
o <2,500 g (5 lb, 8 oz) = low birth weight
o <1,500 g (3 lb, 5 oz) = very low birth weight
 IUGR – babies who are pathologically small
 SGA – babies who are below the 10th percentile in weight
for their gestational age
 Slowdown in growth of head
o 3rd month – ½ of the CRL
o 5th month – 1/3 of CHL
o birth – ¼ of CHL
 5th month –
o the mother starts recognizing fetal movements
clearly
o fetus is covered with fine, small hair
 A fetus born during the 6 th month or start of 7 th month will
have a hard time surviving.
o Why? Because the respiratory and CNS systems
have not differentiated enough.
 Length of pregnancy (full-term fetus) = 280 days or 40
weeks after onset of last menstruation
o 266 days or 38 weeks after fertilization (to be
more accurate)
FETAL MEMBRANES AND PLACENTA
 PLACENTA has two parts:
o FETAL PORTION – from the chorion frondosum
or villous chorion
o MATERNAL PORTION – from the decidua
basalis
  The space between the chorionic and decidual plates is CHAPTER 9—BIRTH DEFECTS AND PRENATAL
filled with intervillous lakes of maternal blood. DIAGNOSIS
o Fetal tissues grow into the maternal blood lakes
and are bathed in them. BIRTH DEFECTS
 The fetal circulation is always separated from the maternal  Approximately 3% of all live-born infants will have a birth
circulation. This is done by: defect.
o SYNCYTIAL MEMBRANE  Various agents and genetic factors are known to cause
o ENDOTHELIAL CELLS congenital malformations.
 Intervillous lakes of the fully grown placenta contain  Agents that cause birth defects (TERATOGENS) include:
approx. 150 mL of maternal blood – renewed 3-4 times per o Viruses
minute. o Radiation
 The villous area facilitates exchange b/n mother and child. o Drugs – thalidomide, aminopterin,
anticonvulsants, antipsychotics, and antianxiety
meds
CHORION FRONDOSUM AND DECIDUA BASALIS o Social drugs – cigs, alcohol
o Hormones
STRUCTURE OF THE PLACENTA o Maternal diabetes
 Human placenta is of the hemochorial type  (See table for more info)
 Functions:  Effects of teratogens depends on:
o Exchange of gases o Maternal and fetal genotype
o Exchange of nutrients and electrolytes o Stage of development when exposure occurs
o Transmission of maternal antibodies (passive o Dose and duration of exposure to agent
immunity)  Major malformations are produced during the
o Production of hormones embryogenesis period
o Detoxification of some drugs  No period of gestation is completely free of risk.

AMNION PRENATAL DIAGNOSIS

 Amnion – a large sac containing amniotic fluid in which  Ultrasound – determines fetal age, growth parameters, and
the fetus is suspended by its umbilical cord detects malformations
 Amniotic fluid:  Maternal serum screening for AFP and other markers – can
o Absorbs jolts detect a neural tube defect
o Allows fetal movements  Maternal serum screening + ultrasound for detecting
o Prevents adherence of embryo to surrounding nuchal translucency – can detect Down syndrome and
tissues other chromosomal abnormalities
 The fetus swallows amniotic fluid (absorbed through gut  Amniocentesis – a needle is placed into the amniotic cavity
and cleared by placenta) and a fluid sample is withdrawn
 Hydramnios (too much amniotic fluid) = anencephaly and o Culture and genetic analysis
esophageal atresia  Chorionic villus sampling (CVS) – involves aspirating a
 Oligohydramnios (not enough amniotic fluid) = renal tissue sample from the placenta
agenesis o Genetic analysis

UMBILICAL CORD FETAL THERAPY

 Umbilical cord contains:  Modern medicine has made the fetus a patient who can
o 2 umbilical arteries receive treatment (transfusions, medications, fetal surgery,
o 1 umbilical vein and gene therapy).
o Wharton jelly (a protective cushion for vessels)
CHAPTER 10: THE AXIAL SKELETON
FETAL MEMBRANES IN TWINS  The axial skeleton includes:
 Vary according to origin and time of formation o Skull
 2/3 of twins are dizygotic (not identical/fraternal): o Vertebral Column
o 2 amnions, 2 chorions, 2 placentas o Ribs
 Monozygotic twins: o Sternum
o 2 amnions, 1 chorion, 1 placenta
 Conjoined twins:  The skeletal system develops from:
o 1 amnion, 1 chorion, 1 placenta o Paraxial Mesoderm
o Lateral Plate Mesoderm
PARTURITION (BIRTH) o Neural Crest
 Preparation for labor begins b/n 34-38 weeks
 Labor consists of 3 stages:  Paraxial mesoderm forms:
o Cervical Effacement and Cervical Dilatation o Somitomeres - in the head region
o Delivery of the Fetus o Somites – from occipital region caudally
o Delivery of the Placenta and Fetal Membranes
 What are somitomeres?
 o Loose cells that come from paraxial mesoderm
and are found alongside the neural tube.
 What are somites???
o They are blocks of mesoderm that are located on
either side of the neural tube.
o They give rise to the parts of the vertebral
column, ribs, skeletal muscles, etc.
o Note that all the segments of somites contain the
same internal structure.
 Somites differentiate into two parts:
o Sclerotome – ventromedial
o Dermomyotome – dorsolateral
 At the end of the 4th week, the sclerotome cells form the
mesenchyme.
o Mesenchyme = embryonic connective tissue
 Mesenchymal cells will differentiate and become:
o Fibroblasts (collagen)
o Chondroblasts
o Osteoblasts (bone-forming cells)
 So basically, all the bones in our body now came from
MESENCHYME.
o Mesenchyme comes from mesoderm and the
neural crest.
 Mesenchyme’s bone-forming ability is not restricted to
sclerotome cells.
o They can also form bones in the parietal layer of
the lateral plate mesoderm (in the body wall).
o The lateral plate mesoderm forms bones of the
pelvic and shoulder girdles, limbs, and sternum.
 Neural crest cells in the head region:
o Differentiate into mesenchyme
o Form bones of the face and skull
 The rest of the skull comes from:
o Occipital somites
o Somitomeres
SUMMARY:
 The skeletal system develops from mesenchyme.
o Mesenchyme comes from:
 the mesoderm (one of the germ layers)
 the neural crest
 Some bones go through intramembranous ossification.
o In this process, mesenchyme cells turn into
osteoblasts (bone) directly.
 However, most bones form from endochondral
ossification.
o In this process, the mesenchyme forms hyaline
cartilage models of bones.
o Bones replace those hyaline cartilage models
eventually.
SKULL
Note:
 Mesenchyme for the skeletal structures comes from:
o Neural crest
o Paraxial mesoderm
o Lateral plate mesoderm
 The skull consists of two parts:
o Neurocranium – case around the brain
o Viscerocranium – forms skeleton of the face
Neurocranium –
 Has two parts:
o Membranous Part – flat bones surrounding the
brain as a vault
o Cartilaginous Part (Chondrocranium) – forms
bones of the skull’s base
 Neural crest cells form the face, part of cranial vault, and
the prechordal part of the chondrocranium.
 Paraxial mesoderm forms the rest of the skull.
Membranous Neurocranium
 Comes from: 1) neural crest cells, and 2) paraxial
mesoderm
 Mesenchyme goes through intramembranous ossification
 Flat, membranous bones
o Presence of bone spicules
Newborn Skull
 At birth, the skull’s flat bones are separated by sutures
 Fontanelles – wide sutures
o Anterior fontanelle – where the 2 parietal and 2
frontal bones meet
 Sutures and fontanelles allow the skull bones to overlap
during birth
Cartilaginous Neurocranium/Chondrocranium
 Base of the skull
 Neural crest cells – form the prechordal chondrocranium
 Paraxial mesoderm (occipital sclerotomes) – form the
chordal chondrocranium
 Endochondral ossification
Viscerocranium
 Face bones
 Formed from the first 2 pharyngeal arches
 First arch – gives rise to the maxillary process (dorsal)
o Max P gives rise to the maxilla, zygomatic bone,
and temporal bone
 Mandibular Process – contains the Meckel cartilage (which
becomes the mandible through intramembranous
ossification)
o Its dorsal tip and the second arch give rise to:
 Incus
 Malleus
 Stapes
o Ossification of these three begins in the 4 th
months (so they’re the first bones to become fully
ossified)
 Mesenchyme for forming bones of the face comes from
neural crest cells
CLINICAL CORRELATES
Neural Crest Cells
 Form the facial skeleton and part of the skull
 Often a target for teratogens
 Craniofacial abnormalities are common birth defects

Cranioschisis
 When the skull/cranial vault fails to form
o Caused by failure of the cranial neuropore to
close
 Anencephaly – caused by cranioschisis and degeneration
of brain tissue
 Severe skull defect = no chance at surviving
 Small skull defects = can be treated
o Cranial Meningocele – meninges herniate
o Meningoencephalocele – brain tissues herniate
Craniosynostosis
 Problems caused by the premature closure of one or more
sutures
 A feature of 100+ genetic syndromes
 Neural crest and mesoderm boundaries are involved
 Craniofrontonasal Syndrome – caused by loss of
function mutations in EFNB1
o Coronal suture synostosis, hypertelorism
 Boston-type craniosynostosis – can affect several sutures;
caused by mutations in MSX2
 Saethre-Chotzen syndrome - coronal suture synostosis
and polydactyly; caused by mutations in TWIST1
 Note: FGFs and FGFRs play important roles in most of
skeletal development.
 Note: Mutations in FGFRs are linked to craniosynostosis
(FGFR1, FGFR2, and FGFR3) and skeletal dysplasia
(FGFR3).
 Scaphocephaly – skull is long and narrow; early closure
of the sagittal suture
 Brachycephaly – short skull; early closure of coronal
sutures
 Plagiocephaly – asymmetric flattening of the skull; early
closure of coronal sutures on ONE side only
 Note: Craniosynostosis is mostly caused by genetic factors
(teratogens; Vitamin D deficiency; intrauterine factors).
Skeletal Dysplasias
 Achondroplasia (ACH) – most common skeletal
dysplasia; affects the long bones; large skull with a small
midface, short fingers, accentuated spinal curvature
 Thanatophoric dysplasia – most common lethal form of
skeletal dysplasia
o Type 1 – short, curved femurs w/ or w/o
cloverleaf skull
o Type 2 – straight, long femurs and severe
cloverleaf skull caused by craniosynostosis
o Cloverleaf skull (kleeblattschädel) – caused by
premature closing of the skull, which leads the
brain to grow through the anterior and sphenoid
fontanelles
 Hypochondroplasia – milder type of ACH
 All of these skeletal dysplasias:
o Autosomal dominant
o Mutations in FGFR3
Generalized Skeletal Dysplasia
 Cleidocranial Dysostosis – dysplasia of osseus and dental
tissues
o Characs: late closure of fontanelles; decreased
mineralization of the cranial sutures 
enlargement of frontal, parietal, and occipital
bones
o Other skeletal parts are affected; the clavicles are
often underdeveloped or missing
Acromegaly
 Caused by congenital hyperpituitarism and too much
production of growth hormone
 Characs: big face, hands, and feet (disproportional to the
body)
 Symmetrical excessive growth and gigantism
Microcephaly
 Brain fails to grow  skull fails to expand
 Intellectual disability (in many cases)
VERTEBRAE AND VERTEBRAL COLUMN
 The vertebral column and ribs develop from:
o SCLEROTOME parts of the somites
 Vertebra parts (basic):
o Vertebral arch
o Foramen
o Body
o Transverse processes
o Spinous process (usually but not all)
 Formation of the Vertebral Column:
o 4th week of development
 Sclerotome cells move to both sides of
the notochord and spinal chord and
merge with other sclerotome cells.
 Sclerotomic segments are separated by
intersegmental mesenchyme/tissue.
o Formation of vertebrae
 Resegmentation - The caudal half of
one sclerotome grows into and fuses
with the cranial half of the subjacent
sclerotome.
 The upper halves of two successive
sclerotomes and the intersegmental
tissue form the vertebra.
 Mesenchymal cells fill the space
between two vertebral bodies –
contributes to the formation of
intervertebral discs.
 The myotomes on both sides of the
vertebrae can move the spine.
 Two primary curves of the spine are
established: THORACIC AND
SACRAL
 (the cervical and lumbar
curvatures develop later)
 NOTE: HOX genes – regulate the patterning of the shapes
of the different vertebrae
CLINICAL CORRELATES
Vertebral Defects (MEMORIZE)
 Scoliosis (lateral curving of the spine)
o Caused by the asymmetrical fusing of two
successive vertebrae or by half a vertebra being
missing
 Klippel—Feil sequence – reduced mobility and short neck
o Caused by fusion of the cervical vertebrae
 Cleft Vertebra (Spina Bifida) – one of the most serious
vertebral defects
o Caused by an imperfect fusion or nonunion of the
vertebral arches
  Spina Bifida Occulta – involves only the bony vertebral
arches—so spinal cord is still intact
o the body defect is covered by skin; no
neurological deficits
 Spina Bifida Cystica – more severe
o Neural tube fails to close
o Vertebral arches fail to form
o Neural tissue is exposed
 Note: Spina bifida can be prevented by giving mothers
folic acid before conception.
RIBS AND STERNUM
 The bony part of each rib comes from the
SCLEROTOME cells in the PARAXIAL
MESODERM.
o These sclerotome cells are the ones that grew out
from the costal processes of thoracic vertebrae.
 Costal cartilages form when sclerotome cells move across
the lateral somatic frontier and into the lateral plate
mesoderm.
 The sternum comes from the LATERAL PLATE
MESODERM in the ventral body wall.
o Specifically – from the parietal layer of lateral
plate mesoderm
 Lateral plate mesoderm forms cartilage models of the
manubrium, sternebrae, and the xiphoid process.
CLINICAL CORRELATES
Rib Defects
 Extra ribs form usually in the lumbar or cervical regions.
 Cervical ribs – attached to C7; 1% of population has this
o May affect the brachial plexus or subclavian
artery  causing anesthesia in the limb
Sternum Defects
 Cleft sternum – arises when the sternal bands fail to grow
together in the midline
o Very rare defect
o May be complete or located at either end of the
sternum
 Hypoplastic ossification centers and premature fusion of
sternal segments:
o Occur in infants with congenital heart defects
 Multiple manubrial ossification centers – common in
Down syndrome patients
 Pectus excavatum – a depressed sternum that is sunken
posteriorly
o Caused by:
 abnormalities of ventral body wall
closure
 abnormalities in formation of costal
cartilages and sternum
 Pectus carinatum – a flattening of the chest bilaterally
with an anteriorly projecting sternum (resembling the keel
of a boat)
o Caused by:
 abnormalities of ventral body wall
closure
 abnormalities in formation of costal
cartilages and sternum
CHAPTER 11: MUSCULAR SYSTEM
 Most muscles come from the MESODERM
o Note: Most because some smooth muscles are
derived from something else.
 Skeletal muscles come from the PARAXIAL
MESODERM, which includes:
1. Somites – form the axial skeleton, body wall, and
limbs
2. Somitomeres – head muscles
 Smooth muscle comes from:
o the splanchnic mesoderm (visceral) around the
gut
o ectoderm
 Cardiac muscle comes from:
o the splanchnic mesoderm (visceral) around the
heart tube
STRIATED SKELETAL MUSCULATURE
 Head muscles come from seven SOMITOMERES
o Note: somitomeres = mesenchymal cells from
paraxial mesoderm
 Somites form:
o Axial skeleton muscles
o Body wall muscles
o Limb muscles
 1) Epithelization – somitomeres undergo this process in
which they form a ball of epithelial cells with a small hole
in the center
 2) Formation of sclerotome from mesenchyme (derived
from each somite’s ventral part)
 3) Formation of dermomyotome (from progenitor muscle
cells)
 4) Formation of infrahyoid muscles, abs, and limb
muscles
o Cells from the VLL region go to the parietal layer
of the lateral plate mesoderm to form these
 4) Formation of back, shoulder girdle, and intercostal
muscles
o The rest of the cells in the myotome form these
Lateral Somitic Frontier – this is between each somite and the
lateral plate mesoderm (parietal layer)
 Lateral somitic frontier – separates two mesodermal
domains in the embryo:
o Primaxial domain – contains only somite-
derived cells
o Abaxial domain – contains somite-derived cells
and lateral plate mesoderm (parietal layer)
 Abaxial muscle cell precursors – migrate across the
lateral somitic frontier and into the lateral plate mesoderm
(its parietal layer)
 Primaxial muscle cell precursors – do not cross the
lateral somitic frontier
 Progenitor cells for muscle tissues come from:
o Ventrolateral (VLL) edge of dermomyotome
o Dorsomedial (DML) edge of dermomyotome
 Cells from both the VLL and DML form the myotome.
Each myotome is innervated by spinal nerves.
 Abaxial muscle precursor cells differentiate into:
o Infrahyoid muscles
o Abdominal wall muscles (RA, E/I Obliques, and
TA)
o Limb muscles
 Primaxial muscle precursor cells differentiate into:
 o Back muscles o Mammary Gland
o Shoulder girdle muscles o Sweat Glands
o Intercostal muscles  Serum response factor (SRF) – transcription factor in
charge of cell differentiation in smooth muscles
INNERVATION OF AXIAL SKELETAL MUSCLES o Myocardin and MRTFs – coactivators which
 Epaxial muscles (back) – innervated by dorsal primary enhance SRF’s activity
rami  Initiate devt. of smooth muscle
 Hypaxial muscles (limbs and body wall) – innervated by
ventral primary rami CLINICAL CORRELATES
 It is common for a muscle to be absent (partial or
SKELETAL MUSCLE AND TENDONS complete).
 During differentiation, myoblasts form long,  Poland sequence – absence of pectoralis minor (complete)
multinucleated muscle fibers. and pectoralis major (partially); serious defect
 End of 3rd month – skeletal muscle’s striations appear o Nipples and areola are absent/displaced
 Tendons – form from sclerotome cells (which lie adjacent o Syndactyly
to myotomes at the front and back parts of somites) o Brachydactyly (short fingers)
o SCLERAXIS – transcription factor which  Prune belly syndrome – absence of abs (partial or
regulates tendon devt. complete)
o Organs are easily palpated
MOLECULAR REGULATION OF MUSCLE DEVELOPMENT o Urinary tract and bladder malformations
 Signals from BMPs (BMP4), FGFs, and WNTs – signal (sometimes)  ab atrophy
VLL cells (of dermomyotome) to express MyoD  Muscular dystrophy – inherited muscle diseases that
o BMP4 – signals production of WNTs cause muscular wasting and weakness
 Signals from neural tube and notochord (SHH and WNTs) 1. Duchenne Muscular Dystrophy (DMD) – most
– induce DML cells common
 MyoD and MYF5 = MRFs (myogenic regulator factors) a. X-linked recessive inheritance (so happens
o They activate pathways for muscle more to males)
development 2. Becker Muscular Dystrophy (BMD) – less severe
3. Note: Both of these are caused by mutations in the
PATTERNING OF MUSCLES gene for dystrophin on the X chromosome.
 CT controls patterns of muscle formation a. Dystrophin links the cytoskeleton to the
 Head Region – CT from neural crest cells extracellular matrix
 Cervical and Occipital Regions – CT from somites
 Body Wall and Limbs – CT from parietal layer of lateral
plate mesoderm

HEAD MUSCULATURE
 All head muscles come from paraxial mesoderm
 CT from neural crest cells control muscle pattern
formations in the head

LIMB MUSCULATURE
 First seen in 7th week of devt
 Mesenchyme forming this comes from somites
 CT – parietal layer of lateral plate mesoderm

CARDIAC MUSCLE
 Formed from splanchnic mesoderm (around the heart
tube)
 Myoblasts stick together  become intercalated discs later
on

SMOOTH MUSCLE
 SM of the dorsal aorta and large arteries – come from:
o Lateral plate mesoderm
o Neural crest cells
 SM of coronary arteries – forms from:
o Proepicardial cells
o Neural crest cells
 SM of gut/gut parts – forms from:
o Splanchnic layer of lateral plate mesoderm
 These are the only SMs which come from ectoderm:
o Pupil