ORGANOGENESIS

Ahmad Azmi Nasution

 7 steps:
1. gametogenesis
2. fertilization
3. cleavage
4. blastulation
5. gastrulation
6. neurulation
7. organogenesis
 Developmental Periods
• Gametogenesis
– Spermatogenesis
– Oogenesis
• Prenatal period (Fertilization)
– Embryo: Zygote
– Cleavage
– Implantation
– Gastrulation…
– Organogenesis
– Fetus
• Postnatal period
– Neonate (<1 month)
– Infancy (< 1 yr)
– Childhood
– Puberty (13 yr – 16 yr)
– Adulthood
Carnegie stages are a system used by embryologists to
describe the apparent maturity of embryos

1st trimester
1st week
 Formation of
Bilaminar Embryonic Disc
Stage 5: 7th –12th day full implantation

2nd week
Stages 6-9: Day 13-21

Somites
3rd week
Stages 10-17

4th to 6th week

7

• Embryo (end of the 8th week)

- all major structures are present
• Fetus (after 8th week)
 Organogenesis
Organogenesis is the formation of organs in their
proper locations
-Occurs by interaction of cells within and
between the three germ layers
-Thus, it follows rapidly on the heels of
gastrulation
-Indeed, in many animals it begins
before gastrulation is complete

12
 Organogenesis
To a large degree, a cell’s location in the
developing embryo determines its fate
At some stage, every cell’s ultimate fate becomes
fixed – cell determination
A cell’s fate can be established in two ways:
1. Inheritance of cytoplasmic determinants
2. Interactions with neighboring cells
-Cell induction
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 Morphogenesis in animals involves
specific changes in cell shape, position,
and adhesion

• Changes in
cell
shape usually
involves
reorganization
of the
cytoskeleton.
• The cytoskeleton is also involved in cell
movement.
– Cell crawling is involved in convergent
extension.
• The movements of convergent extension probably
involves the extracellular matrix (ECM).
• ECM fibers may direct cell movement.
• Some ECM substances, such a
fibronectins, help cells move by
providing anchorage for crawling.
• Other ECM substances may inhibit
movement in certain directions.
 • Cell adhesion molecules
(CAMs): located on cell surfaces
bind to CAMs on other cells.
–Differences in CAMs regulate
morphogenetic movement and tissue
binding.

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 • Cadherins are also involved in
cell-to-cell adhesion.
–Require the presence of calcium for
proper function.

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 The developmental fate of cells
depends on cytoplasmic determinants
and cell-cell induction: a review
• In many animal species (mammals may be a
major exception), the heterogeneous
distribution of cytoplasmic determinants in
the unfertilized egg leads to regional
differences in the early embryo

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• Subsequently, in induction,
interactions among the embryonic
cells themselves induce changes in
gene expression.
– These interactions eventually bring about
the differentiation of the many
specialized cell types making up a new
animal.

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  An example of the molecular basis of
induction:
 Bone morphogenetic protein 4 (BMP-4) is
a growth factor promoting promote the
formation of bone and the skeleton
– In amphibians, organizer cells inactivate BMP-4
on the dorsal side of the embryo.
– In humans it’s a critical signaling molecule
required for the early differentiation of the embryo
and establishing of a dorsal-ventral axis

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 Fate mapping can reveal cell
genealogies in chordate embryos
• Fate maps illustrate the developmental
history of cells.
• “Founder cells” give rise to specific tissues in
older embryos.
• As development proceeds a cell’s
developmental potential becomes
restricted.

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 Fig. 47.20
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 The eggs of most vertebrates have
cytoplasmic determinants that help
establish the body axes and differences
among cells of the early embryo

• Polarity and the Basic Body Plan.

– In mammals, polarity may be established by the
entry of the sperm into the egg.
– In frogs, the animal and vegetal pole determine
the anterior-posterior body axis.

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• Restriction of Cellular Potency.
– The fate of embryonic
cells is affected by
both the distribution
of cytoplasmic
determinants and
by cleavage pattern.

Fig. 47.21

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 Inductive signals drive differentiation
and pattern formation invertebrates
• Induction: the influence of one set of cells on
a neighboring group of cells.
– Functions by affecting gene expression.
• Results in the differentiation of cells into a
specific type of tissue.

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• The “Organizer” of Spemann and Mangold.
• Grafting the dorsal lip
of one embryo onto
the ventral surface of
another embryo
results in the develop-
ment of a second
notochord and neural
tube at the site
of the graft.
– Spemann referred
to the dorsal lip
as a primary
organizer.
Fig. 47.22
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 BMP in neural tube
formation
1. Inhibition of BMP signaling
2. At end of neurulation the
lateral edges of the neural
plate fuse
3. They segregate from the
non-neural epithelia to
form a neural tube
4. Roof plate of neural tube
now produces BMP. BMP
stimulates neural crest cell
formation
• Pattern Formation in the
Vertebrate Limb.
–Induction plays a major role in
pattern formation.
• Positional information, supplied by
molecular cues, tells a cell where it is
relative to the animals body axes.

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• Limb development in chicks as a model of
pattern formation.
• Wings and legs begin as limb buds.
– Each component
of the limb is
oriented with
regard to
three axes:
– Proximal-distal
– Anterior-posterior
– Dorsal-ventra.

Fig. 47.23b
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  Organizer regions.

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• Apical ectodermal ridge (AER).
– Secretes fibroblast growth factor (FGF)
proteins.
– Required for limb growth and patterning along
the proximal-distal axis.
– Required for
pattern formation
along the
dorsal-ventral
axis.

Fig. 47.23a

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 • Zone of polarizing activity (ZPA).
–Secretes Sonic hedgehog, a protein
growth factor.
–Required for pattern formation of the limb
along the anterior-posterior axis.

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 • Homeobox-containing (Hox) genes
play a role in specifying the identity of
regions of the limb, as well as the body
as a whole.
–In summary, pattern formation is a
chain of events involving cell
signaling and differentiation.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

 Organogenesis in Drosophila
Salivary gland development
-The sex combs reduced (scr) gene is a
homeotic gene in the Antennapedia complex
-Prior to organogenesis, it is expressed
in an anterior band of cells
-At the same time, Decapentaplegic protein
(Dpp) is released from dorsal cells
-Forms a gradient in the dorsal-ventral
direction
39
 Organogenesis in Drosophila
Salivary gland development
-Dpp inhibits formation of salivary gland
rudiments
-Thus, during organogenesis, salivary glands
develop in areas where Scr is expressed and Dpp
is absent

40
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Prior to Organogenesis

Dpp

a.

During Organogenesis

Salivary
gland
Labium

b. 41
 Organogenesis in Vertebrates
Organogenesis in vertebrates begins with the
formation of two structures unique to chordates
-Notochord
-Dorsal nerve cord
-Its development is called neurulation

42
 Development of Neural Tube
The notochord forms from mesoderm
-Region of dorsal ectodermal cells situated
above notochord thickens to form the neural
plate
-Cells of the neural plate fold together to
form a long hollow cylinder, the neural
tube
-Will become brain and spinal cord

43
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Neural plate
Amniotic
cavity
Ectoderm
Mesoderm Notochord
Endoderm
Yolk sac

a.

Neural groove
Neural fold

Ectoderm
Mesoderm Notochord

Endoderm

b.

Neural tube

Neural crest
Ectoderm
Mesoderm
Endoderm Somite

44
c.
 Generation of Somites
Mesoderm sheets on either side of notochord
separate into rounded regions called
somitomeres
-These separate into segmented blocks called
somites
-Form in an anterior-posterior wave with
a regular periodicity
-Ultimately give rise to skeleton,
muscles and connective tissues
45
 Generation of Somites
Mesoderm in the head region remains connected
as somitomeres
-Form muscles of the face, jaws and throat
Some body organs develop within a strip of
mesoderm lateral to each row of somites
-Remainder of mesoderm moves out to
surround the endoderm completely
-Mesoderm separates into two layers
-Coelom forms in between 46
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Chorda-
Notochord
mesoderm

Kidney
Intermediate
mesoderm
Gonads

Circulatory
system

Lateral plate Linings of

mesoderm body cavities

Extra-
embryonic

Head
Paraxial
mesoderm
Somite

Cartilage Skeletal Dermis

muscle
47
 Neural Crest Cells
Neurulation occurs in all chordates
However, in vertebrates it is accompanied by an
additional step
-Just before the neural groove closes to form
the neural tube, its edges pinch off, forming a
small cluster of cells called the neural crest
-These cells migrate to colonize many
different regions of developing embryo

48
 Neural Crest Cells
Neural crest cells migrate in three pathways
-Cranial neural crest cells are anterior cells that
migrate into the head and neck
-Trunk neural crest cells are posterior cells that
migrate in two pathways
-Ventral pathway cells differentiate into
sensory neurons and Schwann cells
-Lateral pathway cells differentiate into
melanocytes of the skin
49
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Epidermis Posterior
Neural tube Lateral Pathway
Cells take a
Neural dorsolateral
crest cells route between
the epidermis
and somites

Ventral Pathway
Cells travel
ventrally
through the
anterior half
Posterior of each somite
somite
Anterior somite
Anterior Aorta Notochord
a.
Ventral Pathway Cell Fates Lateral Pathway Cell Fates

Melanocytes
Dorsal root
ganglia
Ventral root
Schwann
cells

Sympathetic
ganglia
Adrenal
medulla

b. 50
 Neural Crest Cells
A mutation in a gene that promotes survival of
neural crest cells produces white spotting on
ventral surfaces of human babies & mice

51
 Neural Crest Cells
Many of the unique vertebrate adaptations that
contribute to their varied ecological roles
involve neural crest derivatives
-For example gill chambers provided a greatly
improved means of gas exchange
-Allowed transition from filter feeding to
active predation (higher metabolic rate)
-Other changes = Better prey detection, and
rapid response to sensory information
52
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Chordates Vertebrates
Zygote
Brain,
Pharynx spinal cord,
Blastula spinal nerves
Lining of
respiratory
tract Endoderm Dorsal Neural
Gastrula Ectoderm
nerve cord crest
Lining of
digestive Epidermis, skin, hair, Gill arches,
tract Major epithelium, inner sensory ganglia,
glands ear, lens of eye Schwann cells,
adrenal medulla
Pancreas Liver
Mesoderm Notochord

Outer covering Circulatory

Integuments system Heart
of internal
organs
Blood Vessels
Lining of
thoracic and
abdominal Gonads Somites Skeleton
cavities
Striated
Kidney muscles
Dermis

53
 Vertebrate Axis Formation
Hans Spemann & Hilde Mangold transplanted cells
of the dorsal lip of one embryo into the future
belly region of another
-Some of the embryos developed two
notochords: a normal dorsal one, and a second
one along the belly
-Moreover, a complete set of dorsal axial
structures formed at the ventral
transplantation site in most embryos
54
 Vertebrate Axis Formation
Donor embryo Recipient embryo Primary Primary notochord, somites,
neural fold and neural development

Dorsal lip

Secondary
notochord, somites,
Secondary and neural
neural fold development

Primary embryo

Secondary embryo

55
 Organizers
An organizer is a cluster of cells that release
diffusible signal molecules, which convey
positional information to other cells
-The closer a cell is to an organizer, the higher
the concentration of the signal molecule
(morphogen) it experiences
-Different morphogen concentrations
stimulate development of different organs

56
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Organ A
Organ B

of morphogen
Concentration
Organ C
Organizer cells
secreting morphogen

Distance from secretion site

Embryo

Decreasing
morphogen
concentration
gradient

57
 Organizers
Creation of the Spemann organizer
-In frogs, as in fruit flies, the process starts
during oogenesis in the mother
-Maternally-encoded dorsal determinants are
localized at the vegetal pole of the unfertilized
egg
-At fertilization, rearrangements in the
cytoplasm cause this determinant to shift
to the future dorsal side of the egg
58
 Animal pole
Pigmented
cortical cytoplasm

Diffuse black
Microtubule
pigment
array

Inner Clear cortical

cytoplasm cytoplasm
Microtubules
Dorsal determinants
Vegetal pole

a.

Point of
sperm entry
Gray crescent

Shifted dorsal
determinants

b.

Organizer
Dorsal mesoderm-
inducing signal
Mesoderm-
inducing signals Nieuwkoop center
(TGF-b family proteins) 59
c.
 Organizers
The maternally-encoded dorsal determinants are
mRNAs for proteins that function in the
intracellular Wnt signaling pathway
-Wnt genes encode a large family of cell-
signaling proteins
-Affect the development of a number of
structures in both vertebrates and
invertebrates

60
 Organizers
Function of the Spemann organizer
-Dorsal lip cells do not directly activate dorsal
development
-Instead, dorsal mesoderm development
is a result of the inhibition of ventral
development

61
 Organizers
The bone morphogenetic protein 4 (BMP4) is
expressed in all marginal zone cells (the
prospective mesoderm) of a frog embryo
-BMP4 is a morphogen that at high levels
specifies ventral mesoderm cell fates
The Spemann organizer functions by secreting
BMP4 antagonists
-Bind to BMP4 and prevents its binding to its
receptor
62
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Animal pole Mesoderm

Epidermal ectoderm
Neural ectoderm
Endoderm

Ventral

Dorsal

Organizer molecules:
Chordin, Noggin, and others

63
Vegetal pole
 Organizers
Evidence indicates that organizers are present in
all vertebrates
-In chicks, a group of cells anterior to the
primitive streak called Hensen’s node functions
like the Spemann organizer
-Secrete molecules that inhibit ventral
development
-Same as those in frog embryos

64
 Induction
Primary induction occurs between the three
primary germ layers
-Example: Differentiation of the central nervous
system during neurulation
Secondary induction occurs between tissues that
have already been specified to develop along a
particular pathway
-Example: Development of the lens of the
vertebrate eye
65
 Induction

Wall of forebrain
Ectoderm Optic cup

Lens Lens Lens

Neural vesicle
cavity Sensory
layer
Pigment Retina
Optic stalk Lens Optic nerve
invagination layer

66
 Human Development
Human development from fertilization to birth
takes an average of 266 days, or about 9
months
-This time is commonly divided into three
periods called trimesters

67
 First Trimester
First month
-The zygote undergoes its first cleavage about
30 hr after fertilization
-By the time the embryo reaches the
uterus, 6-7 days after fertilization, it has
differentiated into a blastocyst
-Trophoblast cells digest their way
into the endometrium in the
process known as implantation
68
 First Trimester
First month
-During the second week, the developing
chorion and mother’s endometrium engage to
form the placenta
-Mom and baby’s blood come into close
proximity, but do not mix
-Gases are exchanged, however

69
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Chorion

Amnion

Yolk sac

Umbilical
cord

Chorionic
frondosum
(fetal)
Decidua Placenta
basalis
(maternal)

Umbilical artery
Umbilical vein
Uterine wall
70
a.
 First Trimester
First month
-One hormone released by the placenta is
human chorionic gonadotropin (hCG)
-Maintains mother’s corpus luteum
-Gastrulation occurs in the second week
-Neurulation occurs in the third week
-Organogenesis begins in the fourth week
-Embryo is 5 mm in length
71
 First Trimester
Second month
-Miniature limbs assume adult shape
-Major organs within abdominal cavity become
evident
-Embryo grows to about 25 mm in length
-Weighs about 1 gm, and looks distinctly
human

72
 First Trimester
Third month
-The ninth week marks the transition from
embryo to fetus
-Nervous system develops
-Limbs start to move
-Secretion of hCG by the placenta declines, and
so corpus luteum degenerates
-Placenta takes over hormone secretion
73
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Increasing Hormone Concentration

hCG Estrogen

Progesterone

0 1 2 3 4 5 6 7 8 9
Months of Pregnancy
74
 Second Trimester
The basic body plan develops further
-Bones actively enlarge in fourth month
-Rapid fetal heartbeat can be heard by a
stethoscope

By the end of the sixth month, fetus is over 30

cm long, and weighs 600 gm

75
 Third Trimester
A period of growth and organ maturation

Weight of the fetus doubles several times

Most of the major nerve tracts in the brain are

formed
-Brain continues to develop and produce
neurons for months after birth
76
 Birth
Estrogen stimulates mother’s uterus to release
prostaglandins, and produce more oxytocin
receptors
-Prostaglandins begin uterine contractions
-Sensory feedback from uterus stimulates
oxytocin release from posterior pituitary
-Oxytocin and prostaglandins further
stimulate uterine contractions

77
 Birth
Strong contractions, aided by the mother’s
voluntary pushing, expel the fetus
-Now called a newborn baby, or neonate

After birth, continuing uterine contractions expel

the placenta and associated membranes
-Collectively called the afterbirth

78
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Intestine

Placenta

Umbilical
cord

Wall of
uterus

Cervix

Vagina

79
 Nursing
Milk production (lactation) occurs in alveoli of
mammary glands when stimulated by the
anterior pituitary hormone prolactin
-Milk is secreted into alveolar ducts
During pregnancy, progesterone stimulates
development of mammary alveoli
-And estrogen stimulates development of
alveolar ducts

80
 Postnatal Development
Growth of the infant continues rapidly after birth
-Babies typically double their birth weight
within 2 months

Different components grow at different rates

-Allometric growth

81
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Fetus Infant Child Adult

Chimpanzee
Human

82