Mammalian Gastrulation and Axis formation

Mammalian Cleavage

Slow and asynchronous, Zygotic gene activated during, 1st meridional as embryo travel to uterus, 2nd is rotational cleavage → one blastomere divided meridionally and other divided equatorially

Compaction

after 3rd cleavage (8 cell stage), blastomeres cluster and form compact ball, outer cell form tight junction and become trophoblast, inner cells form gap junction (signalling) and become inner cell mass

Cavitation

Trophoblast secrete fluid to form cavity, trophoblast transport sodium ion into cavity that osmotically draws water, creates and enlarges the blastocoel, ICM position on 1 side forming mammalian blastocyst

Hatching

timing is critical, blastocoel fuel pressure the trophoblast against zona pellucida, Uterine secrete protease that digest zona pellucida, Lytic enzymes from trophoblast cause zona to rupture

4 steps on implantation

Apposition, Adhesion, Progression (invasion), Decidualization

Apposition

orients blastocyst (ICM face uterus), recognition between trophoblast and uterine cell → by L-selectin and its lignands

Adhesion

Leukemia inhibitory factor (LIF) secreted by epithelial clls, attract embryo to region where adhesion is strongest, adhesion forms by integrins

Progression (invasion)

trophoblast secrete metalloproteinase, digest ECM of uterine cells, embryo embeds into uterine cells, Syncytiotrophoblast form to maintain pregnancy (secrete hormones)

Decidualization

Stromal cells form spongy core → physical/chemical support (cushion), Uterine cells suppress immune responses

ICM into 2 layer

Hypoblast → lower layer/endoderm, Epiblast → upper layer

Hypoblast

primitive endoderm, positioning site of gastrulation, regulate cell movement, promote maturation of blood cells

Bilaminar germ disc

forms from epiblast and hypoblast

Amniotic fluid

secreted from completed amniotic cavity, prevent embryo from drying out, serves as shock absorber

Primitive streak

posterior end of embryo, where gastrulation begins

EMT to mesoderm ingression

epiblast cell though to replace hypoblast cells (contribute to yolk sac lining) → undergo epithelial-mesenchymal transition, ingression cell form mesodermal layer, migrate through primitive streak → form node

Node

thickened bulb at anterior end of primitive streak, from ingression mesodermal cell that migrate through the primitive streak, secrete Chordin

Mammalian anterior-posterior axis formation

primitive streak establishes, 2 signalling centers → Node and AVE (anterior Visceral Endodermal)

Anterior Visceral Endodermal (AVE)

DVE cells express Cerberus to block Nodal and Wnt(3 don’t affect anterior side), migrate anterior to become AVE, produce Dickkopf (wnt antagonist)

BMP4

from the trophoblast, induce epiblast to produce Nodal and Wnt3 at posterior end, lead generation of mesoderm and formation of Node

Paralogues

gene that are similar because of gene duplication event in ancestral species

HOX code hypothesis

evolutionary conservation, paralogues, genes that provide segmental or regional identity along A-P axis, code for Hox gene expression → determines type of vertebra formed, comparative anatomy studies (mouse and chick similar but distribute differently)

Mammalian Hox genes

Sequential activation (Hox1 to Hox13) during gastrulation as primitive streak established, Hoxa1/b1 most sensitive to Wnt and appear first, Regional identity along A-P axis determined by most posterior (posterior dominance)