L4 Human Developmental Genetics 1 Flashcards
From ovulation to implantation
see onenote
Formation of the female pronucleus
see onenote
Fertilisation
see onenote
- Sperm and oocyte plasma membranes fuse delivering the male pronucleus into the oocyte
- rapid release of enzymes from egg which modify the surface so other sperm can’t enter
- oocyte undergoes second meiotic division
- fusion of male and female pronuclei produces first diploid cell - zygote, one-celled embryo
Cleavage forms the morula
see onenote
8 cell stage - morula
key features of epithelial cells
see onenote
- tight (occluding) junctions
- adherence junctions
apical side faces the lumen
tight junctions
provide barrier that prevent water and solutes from passing from one side of an epithelial layer to the other
adherens junctions
provide strong adhesion that connects to the actin cytoskeleton and gives the epithelium mechanical strength
Morula compaction and polarisation
see onenote
compaction - cells start to maximise their contact with each other via cell adhesion molecule, Ecadherin
polarised - along apical-basal axis
creating inner and outer cells
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
first major cell lineage split
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
formation of the blastocyst
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
anatomy of blastocyst
see onenote diagram
cells of the blastocyst:
1. Trophectoderm - will give rise to extraembryonic tissues such as the placenta
- Inner cell mass - will give rise to the embryo
Humans hatch
see onenote
blastocyst breaks out of zona pellucida, can now make cellular contact with epithelium of uterine wall (endometrium)
Epiblast or hypoblast
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
- epiblast
epiblast and hypoblast genetic differences
see onenote
NANOG => epiblasts
GATA6 => hypoblasts
Gene regulatory interactions between epiblast and hypoblast cells
see onenote
Epiblast cells can be cultured as ES cells
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
Formation of amniotic cavity
see onenote slides
forms within epiblast cells while hypoblast cells extend around the inside of the trophoblast to form the primitive yolk sac
Following implantation
after hatching, blastocyst implants into the wall of the uterus
gastrulation and the primitive streak
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
Mouse embryo vs human embryo
see onenote
Model for the formation of the endoderm
see onenote
Actual formation of endoderm
see onenote
endoderm is a mixed population; mix of original hypoblast cells and the epiblast cells that have come through the primitive streak
Formation of the mesoderm gives us the three primary germ layers
see onenote
epiblasts coming through the primitive streak take on a mesodermal fate
- ectoderm - formed from epiblasts that don’t go through the primitive streak, gives rise to skin and nervous system
- endoderm gives rise to gut and organs e.g. lungs
- mesoderm gives rise to muscle, heart and connective tissue
- Mesodermal cells migrate into the embryo
EMT in the mouse primitive streak
see onenote slides
Fgfr1 is required for repression of ECadherin and migration
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
Final pathway
see onenote diagram
