Lecture 6: building embryos Flashcards
Building embryos pathway:
-Zygote
-Blastocyst
–>PSCs –> different cell types
OR –> post-implantation epiblast –> Gastrulations etc
Central problem with building embryos
transition from single cell zygote to a complex organism is complex
what processed does building an embryo involve?
- cleavage
- pattern formation
- morphogenesis
- Growth
- cell differentiation
These processed are not ness. sequential and not independent
cleavage:
cell division without increase in cell mass
Pattern formation:
laying down the spatio-temporal pattern in an embryo
morphogenesis
major changes in 3d for of an embryo
cell differentiation
process whereby cells become structurally and functionally different
primordial germ cells are from
the proximal epiblast
early mouse development:
- one cell
- two cell
- eight cell (non-compacted)
- Early morula. (eight cell, compacted)
- Morula is where the first changes become apparent. Cells on the outside become different to those on the inside
- Embryonic stem cells come from the epiblast
- Cells taken from an early blastocyst are manipulated to try and make them mimic what happens in an epiblast
- Mouse development different to primates
early mouse development: inner cells –>
inner cells –> epiblast ( a subset) –> Embryo
early mouse development: outer cells –>
extra-embryonic (placenta)
early mouse development gastrulation:
produces 3 germ layers.
- ectoderm: skin, nervous system
- mesoderm: muscle, heart, blood
- endoderm: gut lining, liver, pancreas
early mouse development: the node gets ___ anterior as the primitive streak extends anteriorly
more
-the head form anterior to the node and notochord
early mouse development: epiblast cells migrate through
the primitive streak.
-emerge as mesoderm and endoderm
gastrulation from a flat bilaminar disc -chicken
- Cells involute through primitive streak
- Cells laminate out and displace hyperblasts to the sides
- Neural tube, somites and notochord are formed from above Henson’s node
- Primitive streak forms the mesoderm and endoderm
what is the key to patterning the germ layers
signalling
what are the four main signalling centres
1) post. epiblast
2) Anterior Visceral Endoderm (AVE)
3) Extra-embryonic endoderm
4) The Node
signalling: BMP4
Gradient of BMP4 -Bmp4 induced Nodal in EPIBLAST -Nodal induces Lefty1 in DVE -Lefty1 gradient restrict Nodal -Note: Bmp4 inhibits any Lefty1 in visceral endoderm LEFTY 1 gets restricted to the DVE
DVE =
Distal Visceral Endoderm
as embryo grows- AVE + DVE pushed …
anteriorly
-Gradient of DKK1from DVE inhibits Wnt
Gradient of Lefty1 from DVE and AVE inhibits Nodal
NET effect: WNT and TGFb signals restricted to posterior epiblast
-Wnt and TGFb signals set up Primitive streak
-Primitive streak starts to elongate
-Node (highest Nodal expression) is where the notochord will start to form
how does the embryology relate to differentiation of pluripotent stem cells
you have to mimic the timing, concentration and ideally the position of these signals
formation of the anterior (head) neural structures:
epiblast on top, hypoblast on bottom.
anterior end AVE forms with rural plate behind. Posterior end - primitive streak forms with node in centre of complex. non-neural ectoderm surrounding rest
neurulation:
neural plate folds o give the neural tube tube
somites:
sclerotomes, myotomes and dermatomes vertebrae , rib cage, skeletal muscle, cartilage, tendons, and skin.
