L4 Human Developmental Genetics 1

Question 1

From ovulation to implantation

Answer 1

see onenote

Question 2

Formation of the female pronucleus

Answer 2

see onenote

Question 3

Fertilisation

Answer 3

see onenote

1. Sperm and oocyte plasma membranes fuse delivering the male pronucleus into the oocyte
2. rapid release of enzymes from egg which modify the surface so other sperm can’t enter
3. oocyte undergoes second meiotic division
4. fusion of male and female pronuclei produces first diploid cell - zygote, one-celled embryo

Question 4

Cleavage forms the morula

Answer 4

see onenote

8 cell stage - morula

Question 5

key features of epithelial cells

Answer 5

see onenote

1. tight (occluding) junctions
2. adherence junctions

apical side faces the lumen

Question 6

tight junctions

Answer 6

provide barrier that prevent water and solutes from passing from one side of an epithelial layer to the other

Question 7

adherens junctions

Answer 7

provide strong adhesion that connects to the actin cytoskeleton and gives the epithelium mechanical strength

Question 8

Morula compaction and polarisation

Answer 8

see onenote

compaction - cells start to maximise their contact with each other via cell adhesion molecule, Ecadherin

polarised - along apical-basal axis

Question 9

creating inner and outer cells

Answer 9

see onenote

symmetrical vs asymmetrical cell divisions

asymmetrical cell division along tangential axis produces polarised outer cell and a new unpolarised inner cell

inner unpolarised cell becomes the inner cell mass

Question 10

first major cell lineage split

Answer 10

see onenote

outer cells become polarised and also start to express Cdx2, inner cells express Oct4 - represents first example of differentiation

mutual repression between Cdx2 and Oct4, common them when cells go down one of two mutually exclusive lineages

Question 11

formation of the blastocyst

Answer 11

outer cells develop tight junctions as they continue to differentiate

tight junctions in combination with Na+ pump draw water into morula which creates an inner fluid filled cavity
=> blastocyst

Question 12

anatomy of blastocyst

Answer 12

see onenote diagram

cells of the blastocyst:
1. Trophectoderm - will give rise to extraembryonic tissues such as the placenta

2. Inner cell mass - will give rise to the embryo

Question 13

Humans hatch

Answer 13

see onenote

blastocyst breaks out of zona pellucida, can now make cellular contact with epithelium of uterine wall (endometrium)

Question 14

Epiblast or hypoblast

Answer 14

see onenote

Cells of inner cell mass make a second choice:
1. hypoblast (primitive endoderm) - organise themselves into an epithelium that faces the blastocyst cavity

2. epiblast

Question 15

epiblast and hypoblast genetic differences

Answer 15

see onenote

NANOG => epiblasts
GATA6 => hypoblasts

Question 16

Gene regulatory interactions between epiblast and hypoblast cells

Answer 16

see onenote

Question 17

Epiblast cells can be cultured as ES cells

Answer 17

At this stage epiblasts can be isolated and cultured indefinitely in vitro as ES cells

pluripotent

express nanog, oct4, Kif4 and sox2 and can remain in stem cell state without differentiating

these are cells that are used to create mouse knockouts and can be used to derive many different types of cells

Question 18

Formation of amniotic cavity

Answer 18

see onenote slides

forms within epiblast cells while hypoblast cells extend around the inside of the trophoblast to form the primitive yolk sac

Question 19

Following implantation

Answer 19

after hatching, blastocyst implants into the wall of the uterus

Question 20

gastrulation and the primitive streak

Answer 20

see onenote

Gastrulation

• first major embryonic event of morphogenesis, defines body axis; anterior-posterior, left-right
• begins with formation of primitive streak, region in which epiblasts cells undergo an EMT and enter into the space between epiblast and hypoblast layers

Question 21

Mouse embryo vs human embryo

Answer 21

see onenote

Question 22

Model for the formation of the endoderm

Answer 22

see onenote

Question 23

Actual formation of endoderm

Answer 23

see onenote

endoderm is a mixed population; mix of original hypoblast cells and the epiblast cells that have come through the primitive streak

Question 24

Formation of the mesoderm gives us the three primary germ layers

Answer 24

see onenote

epiblasts coming through the primitive streak take on a mesodermal fate

1. ectoderm - formed from epiblasts that don’t go through the primitive streak, gives rise to skin and nervous system
2. endoderm gives rise to gut and organs e.g. lungs
3. mesoderm gives rise to muscle, heart and connective tissue
   - Mesodermal cells migrate into the embryo

Question 25

EMT in the mouse primitive streak

Answer 25

see onenote slides

Question 26

Fgfr1 is required for repression of ECadherin and migration

Answer 26

Normally mesodermal cells downregulate Ecadherin as they undergo EMT and migrate away

In fgfr1- mutatns Ecadherin is not downregulated and the mesodermal cells remain stuck around the primitive streak

Question 27

Final pathway

Answer 27

see onenote diagram