Embryology Lecture 3 Weeks 2 and 3 Flashcards
In week 2:
The implanted embryo becomes more ______ in the endometrium
Further development of _______ into the placenta
Development of a ______, ______, and _______
deeply implanted
trophoblast
bilaminar embryo, amniotic cavity and yolk sac
What happens during bilaminar disc formation?
Trophoblast further differentiates and invades into maternal tissue:
Cytotrophoblast: stem cell population for the placenta
Syncytiotrophoblast: Invasive, fused cells. Derived from cytotrophoblast
Breaks maternal capillaries, trophoblastic lacunae then fill with maternal blood
Secretes human chorionic gonadotropin (hCG)
8.5.6
How does the bilaminar disc form in day 8?
¨Epiblast contributes to forming the overlying amniotic membrane and amniotic cavity (columnar)
¨Hypoblast contributes to forming the underlying primitive yolk sac/exocelomic cavity (cuboidal)
Cells derived from the primitive yolk sac cells (hypoblast cells) form a fine, loose connective tissue called _______
Spaces appear in extraembryonic mesoderm, coalesce to form ______
Chorionic cavity surrounds whole part of embryo except where the embryo is attached to the cytotrophoblast by ______
extraembryonic mesoderm
extraembryonic coelom (chorionic cavity)
connecting stalk
The extraembryonic mesoderm now has 2 components, what are they?
lining the cytotrophoblast and amnion:
extraembryonic somatic mesoderm
covering the yolk sac:
extraembryonic splanchnic membrane

What are the 3 main events of Day 13
Formation of chorion and primary chorionic villi
Formation of chorionic cavity
Formation of the definitive yolk sac
¨Cytotrophoblasts proliferate into the syncytiotrophoblast and form ______
Exocoelomic cavity (primitive yolk sac) lined by new hypoblast cells gets replaced with a ______
Some of hypoblast cells near future mouth proliferate and form ______
primary chorionic villi
smaller definitive yolk sac or the secondary yolk sac
anterior visceral endoderm

The ___ is formed by the extraembryonic mesoderm
connecting stalk
Note: The extraembryonic coelom expands to form a large cavity, within which the embryo and the attached amniotic cavity and yolk sac are suspended by the body stalk (connecting stalk) from which the umbilical cord forms

The posterior wall of the yolk sac forms a small diverticulum which is called ______ and extends into the connecting stalk
allantois

Summary of Week 2 events
Embryoblast forms 2 layers
§Epiblast
§Hypoblast
Trophoblast differentiates into 2 layers
§Cytotrophoblast
§Syncytiotrophoblast
Extraembryonic mesoderm splits into 2 layers
§Somatic
§Visceral
2 cavities form
§Amniotic cavity
§Chorionic cavity
Appearance of primary chorionic villi
Anterior visceral endoderm
Establishment of cranio-caudal axis of development
Completion of implantation
What can low hCG or high hCG mean during early pregnancy?
Low hCG may predict a spontaneous abortion or may indicate an ectopic pregnancy
High hCG may indicate a multiple pregnancy, hydatidiform mole, or gestational trophoblastic neoplasia
____ is marked benign enlargement of chorionic villi (trophoblast) and is characterized by grapelike vesicles in uterus and absence of embryo, high hCG level.
Hydatidiform Mole
Gestational trophoblastic neoplasia (choriocarcinoma)
Malignant tumor of trophoblast
Some times they metastasize to liver and other organs (prognosis poor)
8.5.6

What is paternal imprinting during hydatiform mole?
What are the 7 main events that occur during week 3 of embryo development?
Bi-laminar germ disc forms the primitive streak
Gastrulation forms tri-laminar embryo
Neurulation or neural induction takes place
Somites are formed
Left-right asymmetry is determined
Cardiovascular development takes place
Extraembryonic spaces (coelom) and primitive placenta (villi) further develop
How do you know between cranial and caudal end?
Connecting stalk on caudal side
How does the primitive streak form?
¨Some of the hypoblast cells near the future mouth proliferate and form anterior visceral endoderm (forms the buccopharyngeal membrane)
¨Soon after formation of anterior visceral endoderm epiblast cells near the tail end proliferate and form primitive streak
Cephalic end of primitive streak:
primitive node: slightly elevated surrounding a small pit: primitive pit

Explain Gastrulation
¨Epiblast cells migrate towards primitive streak, detach and slip beneath it
¨Some of the slipped epiblast cells displace hypoblast and form endoderm, others come to lie between epiblast and endoderm to form mesoderm, remaining epiblast cells form the ectoderm

True or False: During gastrulation all germ layers develop from hypoblast
False, epiblast
True or False: At gastrulation, primitive endoderm is replaced by definitive or embryonic endoderm then mesoderm is formed
True
Gastrulation Summary

Intraembryonic mesoderm migrates all over the embryo in between ectoderm and endoderm except at ________ membrane and _______.
buccopharyngeal and cloacal (anal) membrane
What are the major signaling centers during gastrulation (understand the structures and mesoderm)

8.5.6
How is the neural plate formed?

8.5.6
How is left-right asymmetry established during gastrulation?
FGF 8 is synthesized by the node and the primitive streak
¨FGF 8 induces expression of Nodal
¨Nodal is restricted to the left side by accumulation of serotonin (5 – HT)
¨SHH and LEFTY 1 prevent nodal expression crossing over to the right side
¨Nodal upregulates LEFTY 2 and PITX 2:
¤PITX2 is the master gene for left sidedness
¤Left sided organs express PITX2 on their left side

What is situs inversus?

8.5.6
What happens if there’s not enough gastrulation?
Caudal Agenesis (sirenomelia)

What happens when there is too much gastrulation?
Sacrococcygeal teratoma

What are the key features of sirenomelia?
hypoplasia and fusion of lower limbs, vertebral anomalies, renal agenesis, imperforate anus, and genital organ anomalies
_______ clusters of pluripotent cells proliferate and form tumors in the region
Sacrococcygeal teratoma
Teratomas can also arise from primordial germ cells that fail to migrate to the gonadal ridge
High doses of ______l during the third week of gestation kills cells in the anterior midline of the germ disc and produce a deficiency of the midline in craniofacial features resulting in _______
alcohol
holoprosencephaly
_____ is fused eyes
_____ is a single nasal opening formed by fusion of lateral nasal processes
Synophthalmia
Proboscis

The primitive node secretes substances e.g. noggin, chordin, and follistatin that allow a region of the ectoderm to develop into ______.
nerve tissue
Explain neurulation: folding of the neural plate
8.5.6
¨Neural plate –> neural groove –> eural folds —> neural tube
¨As neural folds close, neural crest delaminates and migrates away
¨Closure happens first in middle of the tube and then zips rostrally and causally
Separates itself from the surface ectoderm

Explain neurulation: folding and closure of the neural plate
Folding and closure of the neural tube occurs first in the cervical region
The neural tube then “zips” up toward the head and toward the tail, leaving two openings which are the anterior and posterior neuropores
The anterior neuropore closes around day 25
The posterior neuropore closes around day 28

Neural tube defects:
______ failure of neural tube closure
______ failure of the anterior neuropore closure
______ failure of posterior neuropore closure and/or vertebral development
8.5.6
Rachischisis (image)
Anencephaly
Spina bifida
NTDs have many genetic and environmental causes, but the strongest correlation is folic acid deficiency

Failure of neuropores to close can cause neural tube defects (image)
anterior neuropore: anencephaly
posterior neuropore: spina bifida

8.5.6
Where is spina bifida most common?
lumbosacral region
Causes defects in spinal cord and bones of the spine
What is the 4th germ layer and how is it formed?
At the time of neurulation, cells at the lateral most edge of the neural plate are induced to form neural crest
The neural crest cells transform from epithelial cells into migratory mesenchymal cells that contribute to forming MANY tissues in the body
Neural crest cells are pluripotential
What are neural crest derivatives?
Dorsal root ganglia
Autonomic ganglia
Adrenal medulla
Schwann cells
Pia-arachnoid sheath
Skin melanocytes
Thyroid parafollicular cells
Craniofacial skeleton
Teeth odontoblasts
Aorticopulmonary septum (spiral septum of heart)
What are the 4 types of mesoderm formed from the primative node?
¨Axial mesoderm: passes through the node and migrates along the midline:
forms the notochord
¨Paraxial mesoderm: passes just caudal to the node and migrates slightly laterally:
Forms vertebral bones and associated cartilage, skeletal muscle, and dermis of the back
¨Intermediate mesoderm: Between paraxial and lateral plate mesoderm:
Forms the gonads, kidneys and the duct system of the male reproductive system
Lateral plate mesoderm: passes more caudal and migrates more laterally:
forms limb bones, circulatory system and body cavity linings

Subdivisions of the 4 mesoderm
Axial mesoderm/Chorda mesoderm
¤notochord
Paraxial mesoderm
¤head mesenchyme
¤somites
sclerotome
myotome
dermatome
Intermediate mesoderm
¤urogenital organs
Lateral plate mesoderm
¤splanchnic (viscera)
¤somatic (body wall)
¤extraembryonic
Summary of Mesoderm

What happens in the paraxial mesoderm?
¨Undergoes segmentation:
Forms somitomeres
First appear in cephalic region and formation proceeds caudally
¨From occipital region
caudally somitomeres organize into somites
¨F_irst somite arises on the 20th day_

True or False: New somites appear in craniocaudal sequence approximately 3 pairs per day until, at the end of 5th week, 42- 44 pairs are present
true
8.5.6
What are the correct somite numbers?
Upper 4 - occipital somites (supplied by XII cranial nerve)
8 cervical
2 thoracic
5 lumbar
5 sacral
8-10 coccygeal
Where does somitogenesis begin?
Somitogenesis begins w/ 8th pair of somitomeres
How does the separation of somites work?
FGF signaling from the node drives proliferation; Retinoic acid from adjacent mesoderm drives differentiation. Because the node is caudal to the forming somites, there is a head-to-tail gradient of differentiation
Proliferating cells express a ligand (called ephrin B1). As cells differentiate, they begin to express an INCOMPATIBLE receptor (called eph A) that causes the differentiating cells to repel the proliferating cells, thus pinching off and forming a new somite

How do epithelial somites then transform back into mesenchyme?
¨Signaling from ectoderm induces dermomyotome
¨Signaling from notochord and neural tube induces sclerotome

How does dermomyotome form dermis and muscle?
¨Dorsomedial portion of dermomyotome influenced by notochord becomes muscle that cannot migrate very far (epaxial muscles of the back)
¨Ventrolateral portion of dermomyotome exposed to high levels of BMP from lateral plate mesoderm, becomes migratory muscle (goes into limbs also “hypaxial” muscles of the lateral and ventral body wall, e.g. “latissimus” and “abdominal muscles”

How many types of sclerotome are there and what do they develop into?
Dorsal sclerotome:
¤Dorsal arch and spinous processes of vertebrae*
Medial sclerotome:
¤Meninges*
Central sclerotome:
¤Pedicles & transverse processes of vertebrae, proximal portions of ribs
Ventral sclerotome:
¤Vertebral bodies and annulus fibrosus of intervertebral disks
Lateral sclerotome:
¤Distal portions of ribs

summary of somite derivatives
¨Somite (Paraxial mesoderm) forms:
¤Sclerotome
¤Dermomyotome
Sclerotome forms:
meninges, vertebrae and ribs
Dermomyotome forms:
Dermis of the back of the body (from dermatome)
Muscles (from myotome)
Intermediate mesoderm develops into the ______
urogenital system
8.5.6
Lateral plate mesoderm divides into ______ and ______mesoderm
somatic and splanchnic
Somatic mesoderm:
Lines body wall (somatic mesoderm + ectoderm = somatopleure)
Splanchnic mesoderm:
Covers endoderm (splanchnic mesoderm + endoderm = splanchnopleure)
8.5.6
Somatic (aka parietal) mesoderm stays with epidermis
Splanchnic (aka visceral) mesoderm stays with endoderm

Blood and blood vessels develop from extraembryonic and lateral plate mesoderm
¨Vasculogenesis: blood vessels arise from “hemangioblasts” that develop into blood cells AND vascular tubes
¨Angiogenesis: growth of new blood vessels from existing ones
¨Vessels from extraembryonic mesoderm go out to placenta and eventually hook up with blood vessels (and the heart) in the embryo that arise from lateral plate mesoderm to establish circulation.
¨2 major phases of hematopoiesis:
¤Embryonic (weeks 1-4) : blood cells arise from yolk sac mesoderm
Definitive (week 4-term): blood cells arise from lateral plate mesoderm in the AGM (aorta-gonad-mesonephros region) that go on to seed the spleen, liver, and then bone marrow with hematopoietic stem cells
Folding of embryo
§Occurs
§Cephalocaudally
§Laterally

How does lateral folding work?
¨Right and left somatic layer of lateral plate mesoderm fuse together ventrally and form rounded body form
¨Yolk sac gets incorporated into body of embryo- primitive gut tube
¨Communication between yolk sac and gut tube - Vitelline duct
What are the simaltaneuous events that happen during the closure of the body wall
Purse string-like
closure of the body
wall
Growth of the
amnion
Regression of yolk
sac
What happens if the body wall does not close properly?
Ectopia cordis:
failure of the thoracic body wall to close

_____ is the failure of the abdominal body wall to close
______ is failure of the pelvic body wall to close
______ is failure of most of pelvic body wall to close
Gastroschisis
Bladder Exstrophy
Cloacal Exstrophy
Summary of Third Week
¨Primitive streak
¨Gastrulation à ectoderm, intraembryonic mesoderm and endoderm
¨Notochord formation
¨Neural tube and neural crest formation
¨Paraxial mesoderm à somites
¨Intermediate mesoderm
¨Lateral plate mesoderm cavitation and intraembryonic coelom formation
¨Angiogenesis and primitive heart tube formation
¨Secondary villi à tertiary villi à placental circulation begins
