Early Human Embryonic Development

Lecture
Early Human Embryonic Development
Learning Objectives
Able to describe human
development in the following
aspects.
Describe the mechanism of
fertilization
Describe the general principle of
human development
Describe the molecular principle of
human development
Describe the general processes of
human development during both
embryonic and fetal stages
Describe the structures and
development of placenta and fetal
membranes
Describe the causes of abnormal
development and their structural
abnormalities
Outline
Fertilization bi zygote
→
Introduction to human
development and Molecular
embryology
First week of human
development
Second week of human
development
Third week of human
development
Fourth to Eighth weeks of human
development AN 8 Juni fetus =
y
Ninth week of human monnialoovde
development to Birth AN rut divine
Placenta and Fetal membranes
Human birth defects
 Fertilization
Ancient views of human embryology
iwoñm :ÑonVreÑm%V + sperm mrniririiwwnoon vinvinspermiriiai:b
Leonardo da Vinci's drawing
in the 15th century

17th-century drawing of
a sperm by Hartsoeker
The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020

vrigenzymeiovi.vn'm
yirindvgirwriiniaiorumi
f n' own's ovum

mitochondria ntwrdv

yñmitrkrownis
osifmrrnoii wni glycoprotein
Jacob Rueff's De Conceptu et
Generatione Hominis (1554)
The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020 Human Molecular Genetics, 5th edn, Strachan-Read, 2019
 Fertilization
Gametogenesis and Meiosis
meiosis linen

spindle Versioning

gzwtsiai rivi s

iirsivd : nah

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

0
misiiriiñasiveñisni meiosis I

own's www.wwoiiijsoioriorioumnii
Isi first polar body

rinn metaphase
10 I

n wd 1-
sperm i fertilize )
b
complete meiosis I

1st second polar body

10 polar body irinmohlu meiosis I

i polar body winnow meiosis #
casts fertilization )
polar body Nurmi Ennis

iwriumdsnnshi oocyte slcyloplasmbvd:

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Fertilization
Spermatogenesis

seminal prostate bulbourethral

, ,

ioiwoiirriiuwiennlwsemen
( lñspemWnu7ñ
BTB -
Joon.ws/7ermvnnhrVYsWdn
oohs sperm lwmrriwluwvnvo.mil

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Fertilization
Spermatozoon

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

spermiogenesis
acrosomeoy IN
'

dcrosomal cap

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Fertilization
Oogenesis @ ovary

spermwivnvn.ca/sacitation@iwrswnopniriamrunfnnldnVoi
glycoprotein yiwacrosome

Unwoven
w .hiwo ripwviamrvaiworynidoniavewtygote (
fimbria nativists / Unions
i. polar
2
'
polar
/ body

body
uterus
www.s.VN

endometrium -
basal layer
L functional
layer
a -1
Wyland worrier
pronucleus
,

uynooonntwvruiwñihi

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Fertilization and Assisted reproductive technologies
Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

Oogenesis

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020

antrum over win ligroin www.wouwj

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Fertilization
Oogenesis

open gap junction → CAMP win → inhibit process of meiosis

FSH LH
, nriryis
follicular cell

atnrndonio hormone rioñir

close gap junction

b

CAMP b

b
meiosis Ivridoñ

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Fertilization
Main events in fertilization
itosñw pdyspermylspemimwlunhvminfnvwntvvfnswr.isevitsrovoocyte

arjhyamlonicacid
I
release cart
Nnivvvruwiwnh
↳ www.o-inhdvuinroain

#
win cortical reaction
tekaseont.VN
receptor oevspem

'nfWfVÑhhh
in
I
monospemy wrhyaluronidase
t acrosome →
release enzyme entymeiovwn.nirnrniv.in
nudeusvviviuri
b
male pronucleus
- uoioaorosin
vivtona pellucida

Wreceptorcheckiipnspeciesw.ir
Human Embryology & Developmental Biology, 6th edn, Carlson, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Fertilization and Assisted reproductive technologies
Acrosome reaction and Zona pellucida

deepfor hisperm recognize

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

uriah iiriniiñsivnñvrnhhi

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Fertilization
Molecular process in fertilization

cortical reaction
VIN en t . in receptor Voom polys per my

release aerosome

Ven Zona pellucida

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Fertilization
Assisted reproductive technologies

ICSI ret sperm Nikki cytoplasm voi oocyte Iñrnvmrs

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
Early Human Embryonic Development
Learning Objectives
Able to describe human
development in the following
aspects.
Describe the mechanism of
fertilization
Describe the general principle of
human development
Describe the molecular principle of
human development
Describe the general processes of
human development during both
embryonic and fetal stages
Describe the structures and
development of placenta and fetal
membranes
Describe the causes of abnormal
development and their structural
abnormalities
Outline
Fertilization
Introduction to human
development and Molecular
embryology
First week of human
development
Second week of human
development
Third week of human
development
Fourth to Eighth weeks of human
development
Ninth week of human
development to Birth
Placenta and Fetal membranes
Human birth defects
 https://www.researchgate.net/profile/Gregory_Podgorski/p
The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020 ublication/262383220/figure/fig2/AS:213959178231822@1
428023252008/Waddington%27s-classic-model-of-an-
epigenetic-landscape-11-A-developmentally-immature.png
yn cell wmirmoohrrfvdnirwmrrnioniwuniuwi.vn
From unicellular zygote to multicellular organism
Introduction to human development
and Molecular embryology
The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Introduction to human development
inhibit HATS ,
Histone kinases
}
and Molecular
DNA nhimirswir =
embryology
heterochromatin
activate HDACs
Ñnvhivri
Epigenetics Umrah / Units

www.wririw
DNA methylate bud : , =

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020

phosphate
acetyl
joinhistone -

acetylene

MovinUAIVVV → DNA nhruwd N

r deacetyl : No acetyl don

lysine arginine
,
( t) in ñv DNA rain c interaction Urey I

lovnvvurionrrrwloi

Human Molecular Genetics, 5th edn, Strachan-Read, 2019

①
acetyl group Dandini Irvine DNA Bowden

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
Human Molecular Genetics, 5th edn, Strachan-Read, 2019
 Introduction to human development
and Molecular embryology
Epigenetics

+ methyl 1- methyl

niumwiwroivv-irrivr.vn cell

-
methyl

Human Molecular Genetics, 5th edn, Strachan-Read, 2019

mriniwunt.me/-hylrienhancersndUqwgene expressionist

Human Molecular Genetics, 5th edn, Strachan-Read, 2019 Human Molecular Genetics, 5th edn, Strachan-Read, 2019
 Introduction to human development
and Molecular embryology
Overview of development

Multicellular organisms Developmental stages

Start from single cell to Embryonic stage:
mature organism establish major organ
Many rounds of cell systems (8 wks in human)
niwvgorwi
lawn

division Postembryonic stage: fetus /

fetal stage

Specialized and organized growth and refinement

in precise patterns (some replenish
throughout life to reach
equilibrium)
 Introduction to human development
and Molecular embryology
Overview of development
Gradual process Development processes
Increased number of cell (separate or combined)
types Cell proliferation: cell
Organization to number, balanced by cell
progressively achieve loss Winwood inner
+

complexity Growth: size and biomass

nioomrriiuuiinio : Ir ←
Differentiation: structurally
and functionally specialized
Pattern formation: form
fundamental body plan &
detailed structures
Morphogenesis: change
shape or form of organism
 Introduction to human development
and Molecular embryology
Underlying mechanisms
Cellular levels Molecular levels
Differential cell proliferation j
by epigenetics

Selective cell-cell adhesion Differential gene expression

Cell-matrix adhesion (when and where?)
Change in cell shape and Cell signaling molecules
size Transcription factors
Control over symmetry and Proteins VS noncoding RNAs
Uni protein translate Nw
plane of cell division
Selective use of
programmed cell death

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Introduction to human development
and Molecular embryology
Intercellular signaling & Molecular regulation
Induction:
Inducer VS Responder ihhtvmriuoivdnh
Competence and Competence Factor
Epithelial Mesenchymal Interactions
Lex dermis lamina
.

,
propia
Intercellular Signaling:
Paracrine Interactions (contact-independent) unis ✓
mitosis ( signaling molecule
Mitogen: cell proliferation my,gwwyµ
monger
Motogen: cell motility
nun

Morphogen: cell differentiation

(concentration and area) ginimirontwworñv
Juxtacrine Interactions (contact-dependent)
Families of paracrine interaction:
1. Fibroblast Growth Factor (FGF)

{
2. Wingless/int (WNT)
3. Hedgehog (HH) ligand
4. Transforming Growth Factor (TGF- )
5. Others: Serotonin, Norepineprhine
Sadler, Medical Embryology, 12th ed
?⃝
 Introduction to human development
and Molecular embryology
Intercellular communication & Signal transduction (RTK)
common signal
Gap junction transduction
RTK
pathway

Mountains riv

Cadherin
NCAM
iv. phis

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Introduction to human development
and Molecular embryology
Intercellular communication & Signal transduction (Delta-Notch & Hippo)

Iahtirrasiv

.io/niowkyvu roivonis-g1iace1l
-

Lateral inhibition
Hippo

ñHippoDMnñw

4 \neuron ñiltippowisnnrvjw
iaihtynmi.wfm.NU neuron
Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

- iruoinihlriyiorg
Delta-Notch
trunking

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Introduction to human development
and Molecular embryology
Families of intercellular signaling molecule

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

in body symmetry givin

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Introduction to human development
and Molecular embryology
Families of intercellular signaling molecule

TGF-

FGF gmouiirnignyivñw pro region

→ oirtv receptor 2 subunits

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

Wnt

B- catenin In release

Unni B- catenin main www.iri

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
Introduction to human development
and Molecular embryology
Drosophila dentricle belts & Hedgehog

Alexandre C et al (1999), Development 126:5689-98

 Introduction to human development
and Molecular embryology
Sonic hedgehog (Shh)

Unni : patched inhibit smoothened

ñÑ shh Nntu : iaiiñnmr inhibit
smoothened Werth cilia
iinknhlvi Glia Marin www.voroivnvhiloi

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Introduction to human development
and Molecular embryology
Transcription factors (TF) → onion domain Ktv DNA

1. Homeodomain
proteins (Homeobox-
containing genes)
Homeobox (Hox) gene
family
Paired (Pax) gene family
Others eg. Lim, Dlx, Msx
2. T-box (Tbx) gene
family

www.ersriw

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Introduction to human development
and Molecular embryology
Transcription factors (TF)

Cooper, The Cell, 4th ed

3. Helix-Loop-Helix TF
Basic H-L-H proteins
Forkhead (Fox) gene family
4. Zinc finger TF I tincñrlñahtnvrvu Nv
fingers Toi n'
NUBWw mins
Sox gene family Mini is win # gig, -

Wilms tumor suppressor 1 (WT1) gene

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

 Introduction to human development
and Molecular embryology
Animal models for study of development

Human Molecular Genetics, Strachan-Read, 4th edn, 2010

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

 Introduction to human development
and Molecular embryology
Animal models for study of development
Conserved for key molecules & PWs among animal evolution
Invertebrate Vertebrate
D. melanogaster: irwaouoi (similar dev. stages phylotypic stage)
neurogenesis, eye D. rerio: genetic approaches,
development transparent embryo
raven
C. elegans: almost invariant X. laevis and avian models:
cell lineage and known fate
'
large external egg Iiwonohomv
of all cells marina miiñwiv Mammalian/primate models:
-

tiny internal egg, closely related

to human N path
yay KNTV

Human Molecular Genetics, Strachan-Read, 4th edn, 2010 Human Molecular Genetics, Strachan-Read, 4th edn, 2010
 Introduction to human development
and Molecular embryology
Cell specialization
ÑswoniwnirNÑv%rÑvstv%w
cell

rhodium won +14

Alternative cell fates
cell
depending on cell position
Symmetrical zygote
asymmetrical organism
3 axes:
position rdvy Symmetrical: lateral halves
venimdrivirxwuei.ir Asymmetrical: dorsal-ventral,
Human Molecular Genetics, 5th edn, Strachan-Read, 2019 or anterior-posterior
Signals from nearby cells as
induction
Inducer Responder
Cell fate depending on position, not
its lineage 2 stages:
Specified: reversible by
environmental induction
Determined: irreversibly committed
by specific molecular process

Human Molecular Genetics, 5th edn, Strachan-Read, 2019

 Introduction to human development
and Molecular embryology
Cell specialization

www.sinmisi uji u iuwlahkir uriviuvjdlsi wa

niuun
Sometimes cell fate specified
by lineage rather than position
Asymmetric cell division of stem
cells different daughter cells
One as parent stem cell for
Human Molecular Genetics, Strachan-Read, 4th edn, 2010
ensuring renewal
The other as committed lineage of
spindle ring
differentiated cells
1 9
Intrinsic or autonomous (non-
conditional) specification of cell
fates ddvqwfnvvw.vnv14
Eccentric positioning of mitotic
spindle niwiuw's spindle
Asymmetric localization of cell
products (eg. regulatory proteins,
upstream polarity regulators): cell
polarity
Human Molecular Genetics, Strachan-Read, 4th edn, 2010
 Introduction to human development
and Molecular embryology
Pattern formation
siri www.iuriworwvririwiu

Body plan depending on axis

specification and polarization
3 axes and polarity:
Symmetrical: lateral halves (L-R)
Asymmetrical:
Dorsoventral (D-V)
Anteroposterior/cranio(rostro)ca
udal (A-P)
Mechanisms of symmetry
breaking:
Presence of egg asymmetry due
to determinants hiii l sins yolkuwhmms.in
-

www.woiwuwlrhi uwjmrhhevds
embryo
External cue: gravity in chickens,
site of sperm entry in frogs
sperm
In mammals: no determinant
identified with developmental
flexibility
Human Molecular Genetics, Strachan-Read, 4th edn, 2010
 Introduction to human development
and Molecular embryology
Pattern formation
Human Molecular Genetics, Strachan-Read, 4th edn, 2010
/ Dorsal
anterior
dbembryonicpde
Medical Embryology, 14th edn, Sadler, 2019
Langman's Medical Embryology, 13th edn, Sadler, 2015
Axis specification and polarity
in early mammalian embryo
Animal-vegetal axis as first
symmetric cleavage
First polarity in blastocyst:
embryonic pole Embryonic pole (ICM) &
abembryonic pole (blastocele) D-
V axis
Primitive ectoderm (epiblast) &
primitive endoderm (hypoblast)
ventral Second axis of A-P depending on:
+ Position of sperm entry
(embryonic-abembryonic border)
Specific area of hypoblast called
anterior visceral endoderm (AVE)
induces anterior ectoderm
Proximal epiblast with mesodermal
gene expression migrates to posterior
end primitive streak
Third axis of L-R in gastrula
depending on: left hand
/ of perinodal fluid
Unidirectional flow
Nodal and Lefty-2 expression in
lt-hand side lt-hand-
specific TF (eg. PitX2)
 Introduction to human development
and Molecular embryology
Pattern formation

Mechanisms for controlling Regionally specific cell

positional identity
Precise position by major axes
as coordinates
Different cell behaviors
Different gene products
Appropriate body plan
behaviors depending on
signal gradient of
morphogens, mainly used
in
A-P axis of body
A-P and proximodistal axes of
limbs
Homeotic gene expression
guided by morphogen
gradient as molecular basis
of positional identity
 Introduction to human development
and Molecular embryology
Homeotic gene complex

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

Homeotic mutations reveal molecular basis of positional identity

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

segmentriw

0 giulia

Gilbert, Developmental Biology, 7th ed

Drosophila mutants of homeotic transformation

Antennapedia: legs growing in place of
antennae www.N.iinwuwm
2 clusters of homeotic genes (homeotic gene
complex, HOM-C) ↳ duqwmrrvrrya P -

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

 Introduction to human development
and Molecular embryology
Homeobox genes

Gene encodes TF with

homeodomain (encoded by
DNA sequence called
homeobox)
Clustered homeobox genes
as Hox genes (functionally
copy said ñvivnlrihi segment iñvdñw
and structurally well
conserved)
4 unlinked clusters of Hox
genes in humans and mice
Differential expression
controlled by morphogens

Human Molecular Genetics, Strachan-Read, 4th edn, 2010

 Introduction to human development
and Molecular embryology
Homeobox genes
Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

www.i-uiswnriummduorwdsoid retinoic acid Minis

- Retinol binding protein

 Introduction to human development
and Molecular embryology
Homeobox genes
Zone of polarizing activity (ZPA) as
source of morphogen gradient
Gradient of morphogen
sensitiveponds Different levels of Hox genes expression
/ Innhrimouoiwoiini
r

sensitive main Different regional cell behavior

ridsiyilbowiwrina .ÑNrwNg

Able to diffuse only a few cell widths

indirect effect
Example of A-P axis formation:
node (ZPA)
Nooioonoisanlai

Increasing Retinoic acid (morphogen)

secretion (then Sonic Hedgehog
(Shh) secretion) as regressing

Progressive activation of more Hox

genes in posterior embryonic regions

Human Molecular Genetics, Strachan-Read, 4th edn, 2010

 Introduction to human development
and Molecular embryology
Homeobox genes/gene classes and Homeodomain proteins
Annual Review of Biochemistry 61: 1053-1095
www.devbio.com after Pabo & Sauer (1992),

Holland PWH et al (2007), BMC Biology 2007, 5:47

Holland PWH et al (2007), BMC Biology 2007, 5:47 Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
 Introduction to human development
and Molecular embryology
Morphogenesis ivdvwiivs.ru/nIuiuwiewu

Morphogenetic process Processes from altered cell adhesion

Change in cell shape Migration UÑWddnan
ninth
Change in cell size Ingression Egression
Gain of cell-cell adhesion www.wrswioeiwrowroiw
Delamination Intercalation
arrow
Loss of cell-cell adhesion Condensation Dispersal
Cell-matrix interaction Epiboly: spreading of a sheet of
Loss of cell-matrix adhesion cells liaiddniihlwhivoscell
Differential rates of cell
proliferation
Alternative positioning and/or
orientation of mitotic spindle
Apoptosis -
rain;
Cell fusion iriaapoptosis
ñnuiirirnñw

Human Molecular Genetics, Strachan-Read, 4th edn, 2010

 Introduction to human development
and Molecular embryology
Basic concepts

form
germ layer
form organs
(embryonic/fetal age)
/ MMM's organs
air

migrations (gestational age)

ÑdJ
Human Embryology & Developmental Biology, 6th edn, Carlson, 2020
HIS

cranial
(4 wks/month)

www.niiofnnyv
The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
ventral dorsal

Embryonic/Fetal age = Gestational age 2 wks

( GA )
caudal
Gestational age 3 trimesters (3 months each)
Imrwnnisirnntirihinfn :
-

window.

The Developing Human: Clinically Oriented Embryology, 11th edn, Moore-Persaud-Torchia, 2020
 Introduction to human development
and Molecular embryology
Basic concepts
I
mesoderm n'Wmtw
neural tube

Irvine Nvq )
'

8 weeks
(embryonic
stage)

Human Embryology & Developmental Biology, 6th edn, Carlson, 2020

Introduction to human development
and Molecular embryology
Basic concepts simile www.rivassmmiwiw

https://web.archive.org/web/20070521214746/http://embryology.med.unsw.edu.au/OtherEmb/CStages.htm#Source