1 - Early Stages of Mammalian Development and Gastrulation

Question 1

Zygote to Blastocyst Development - Cleavage

Answer 1

A series of mitotic divisions where the embryo increases in cell number but not in size.

Question 2

Blastomeres

Answer 2

(2-8 cell stage) remain totipotent

Question 3

Blastomeres Evidence for equivalence

Answer 3

Blastomeres can be removed without affecting development (basis for preimplantation genetic testing).

Question 4

Compaction (8-cell stage)

Answer 4

Cells maximize contact, forming a morula

Requires E-cadherin, a cell adhesion molecule

Question 5

First differentiation event

Answer 5

Outer cells → Trophectoderm (barrier function, placenta precursor)

Inner cells → Inner Cell Mass (ICM) (embryonic tissue precursor)

Question 6

Epithelial Formation in Early Development - Trophectoderm

Answer 6

first epithelial layer, characterized by: Apical-basal polarity (different proteins at apical vs. basal sides)

Question 7

Barrier function

Answer 7

separates embryo from external environment

Question 8

Ion transport

Answer 8

Sodium ions pumped inside, leading to fluid accumulation (blastocoel formation)

Question 9

Transcription Factors Determining Inner Cell Mass Identity (before compaction)

Answer 9

All cells express Oct4 and Cdx2

Question 10

Transcription Factors Determining Inner Cell Mass Identity (after compaction)

Answer 10

Outer cells → Higher Cdx2 → Trophectoderm

Inner cells → Higher Oct4 → Inner Cell Mass

Question 11

Mutual inhibition ensures cell fate

Answer 11

Cdx2 represses Oct4 → Trophectoderm formation

Oct4 represses Cdx2 → Inner Cell Mass maintenance

Question 12

Mutual inhibition ensures cell fate (loss of Cdx2)

Answer 12

Trophectoderm fails to develop → No blastocyst formation

Question 13

Blastocoel formation

Answer 13

Sodium pumps in trophectoderm drive osmotic water influx

Water accumulation enlarges the blastocoel cavity, leading to blastocyst formation

Question 14

The primitive endoderm forms from

Answer 14

ICM cells adjacent to blastocoel

Question 15

Trophectoderm-derived signals induce differentiation

Answer 15

Parathyroid hormone-related peptide (PTHrP) from trophectoderm induces parietal endoderm

Bone morphogenetic proteins (BMPs) from epiblast induce visceral endoderm

Question 16

Parietal Endoderm

Answer 16

Secretes extracellular matrix proteins → Forms Reichert’s membrane

Prevents maternal cells from invading and destroying the embryo

Question 17

Visceral endoderm

Answer 17

Provides nutrients before placenta formation

Secretes signals that regulate epiblast differentiation

Question 18

Position dependant differentiation (cells near mural trophectoderm)

Answer 18

Parietal endoderm (PTHrP signaling)

Question 19

Position dependant differentiation (cells near epiblast)

Answer 19

Visceral endoderm (BMP signaling)

Question 20

Preparing fro gastrulation (epiblast polarisation)

Answer 20

Signals from basement membrane induce cell polarity

Leads to formation of the proamniotic cavity

Question 21

Anterior-Posterior Axis Formation

Answer 21

Defined by anterior visceral endoderm (AVE) movement

AVE secretes inhibitors of gastrulation, ensuring it occurs at the posterior end

Question 22

Lim1

Answer 22

Transcription factor

Crucial for head and brain development

Question 23

What is gastrulation

Answer 23

A critical phase where the embryo reorganizes to form three germ layers
- Ectoderm
- Mesoderm
- Endoderm

Question 24

3 germ layers

Answer 24

Ectoderm → Skin, nervous system

Mesoderm → Muscle, bones, cardiovascular system

Endoderm → Digestive and respiratory systems

Question 25

Primitive streak formation

Answer 25

Marks the site where epiblast cells migrate inward Cells undergo epithelial-to-mesenchymal transition (EMT) to move

Question 26

Role of Cell-Cell Adhesion in Gastrulation - Epithelial-Mesenchymal Transition (EMT)

Answer 26

Requires downregulation of E-cadherin (cell adhesion protein) Allows epiblast cells to detach and migrate through the primitive streak

Question 27

Role of Cell-Cell Adhesion in Gastrulation - β-Catenin

Answer 27

Adhesion - Links cadherins to the cytoskeleton Signalling - Moves to the nucleus to activate key genes for mesoderm formation

Question 28

Key genes in EMT

Answer 28

Twist Snail

Question 29

Twist

Answer 29

Required for mesoderm formation

Question 30

Snail

Answer 30

Moves to the nucleus to activate key genes for mesoderm formation

Question 31

Formation of the Anterior-Posterior Axis

Answer 31

AVE movement defines anterior identity AVE secretes gastrulation inhibitors to ensure the primitive streak forms at the posterior end Lim1 expression in AVE is critical for brain developmen

Question 32

Role of β-Catenin in Gastrulation

Answer 32

Mechanical pressure → β-catenin translocates to nucleus → Turns on genes for invagination Loss of β-catenin leads to gastrulation defects

Question 33

Importance of Transcription Factors & Signaling

Answer 33

Fibroblast Growth Factor (FGF) Signaling - Controls EMT at the primitive streak FGF inhibition prevents cells from migrating → No mesoderm/endoderm formation

Question 34

Brachyury

Answer 34

Essential for mesoderm differentiation. Loss of Brachyury leads to caudal dysgenesis (trunk and tail malformations)

Question 35

Gastrulation Defects in Humans

Answer 35

Caudal dysgenesis (sirenomelia) caused by insufficient mesoderm formation Affects limb, urogenital system, and vertebrae development