BIOL 303 Lecture Notes - Lecture 8: Cdx2, Morula, Trophoblast
14 May 2018
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Biol 303 March 1st
Axis formation in Mice – vertebrates
• The time scale of embryo formation has units of days (rather than hours/minutes as in
other model organisms)
• What happens in the first 6 and a half days from fertilization to gastrulation and
formation of the posterior-anterior axis
Mice as a model organism
• Mice are used as a model because they resemble humans (are mammals)
• It is easy to edit their genome
How does early embryogenesis start?
• The egg will extrude an egg/oocyte into the fallopian tube where it is fertilized by the
sperm
• We normally mate male and females in a cage and leave them overnight → the next day
at oo is alled da 0.5 eause e assue the opulated aoud idight
• Days are given as 1.5, 2.5, etc.
• The fertilized embryo goes down the fallopian tube and undergoes cleavage as it travels
• Each cell is called a blastomere in the cleavage stage
• The 2-cell embryo is going to be formed at day 1.5
• (in other species you would be done development by this time point)
• Morula: a compact mass of cells (8-16 cells)
• Things go a bit quicker after day 2.5 at the morula stage
• At day 3.5, the embryo enters into the uterus
• For it to continue its embryonic development, it needs to implant into the uterus
• Implantation occurs on day 4.5 in the uterus
• The embryo is at the blastocyst stage when it enters the uterus
Preimplantation development
• Cell adhesion has changed from the
morula (8 cells/blastomeres) to the
compacted morula (also 8
cells/blastomeres) so it looks different
but is still the same number of cells
• At the compact morula, cells have to
decide what cell type they will be
• ICM = inner cell mass - a cluster of cells
at one pole (no anterior/posterior fate
yet) – all of the embryo tissue derives
from this
• Trophectoderm – lines the outside of
the embryo – becomes the placenta
find more resources at oneclass.com
find more resources at oneclass.com
• The ICM is composed of the primitive endoderm and the Epiblast:
• PE = primitive endoderm – gives rise to the yolk sac (an extraembryonic tissue)
• EPI = Epiblast – gives rise to the germ layers and germ cells
• Inside cells give rise to the inner cell mass (ICM)
• Outside cells form the trophectoderm
Cell polarity Model
• Knockout experiments of genes in the mouse embryo helped us understand how this
polarity was determined
• It is transcription factors that play an important role
• Oct4 and Nanog, have a similar pattern of expression, are expressed in all cells in the
early embryo
• Cdx2 and Oct4 are both expressed in all cells at the 8-cell stage
• Cdx2 – only expressed in the outer cells of the morula by the 16-cell stage
• Later on: Gata6 and Nanog start playing a role in the blastocyst stages
Hippo signalling pathway
• A relatively new pathway – determines the size of organs
• Hippo activation leads to Lats and Yap activation → Yap goes to the nucleus and
activates Tead4 which leads to the transcription of Cdx2
• When Yap is phosphorylated it is silenced and does not lead to transcription (this occurs
i ie ells eause the dot hae the oute fate that is otolled Cd2
Oct4 and Cdx2 reciprocal repression
• Oct4 knockout: you just get TE
• Cdx2 knockout: all cells become ICM
• Cdx2 represses expression of Oct4 and Nanog in TE cells
• It comes down to influencing FGF signalling
• Some cells express FGF4 and other cells express the FGF4 receptor
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Mice as a model organism: mice are used as a model because they resemble humans (are mammals) Implantation occurs on day 4. 5 in the uterus. Inside cells give rise to the inner cell mass (icm) Cell polarity model: knockout experiments of genes in the mouse embryo helped us understand how this polarity was determined. Oct4 and cdx2 reciprocal repression: oct4 knockout: you just get te, cdx2 knockout: all cells become icm, cdx2 represses expression of oct4 and nanog in te cells, some cells express fgf4 and other cells express the fgf4 receptor. It comes down to influencing fgf signalling: those with the fgf4 receptor express gata6. Migration of endoderm at the distal tip: ave = anterior visceral endoderm crucial for ap patterning of the embryo, a gene marked by gfp is followed. In situ hybridization experiment (purple label: lots of gene show the same pattern of expression as hox genes ex.
