Genetic and environmental influences of human dev Flashcards
most trisomy 21 arise from non-disjunction in ____ and produces____
meiosis 1 and produces gametes with 2 copies of chromosome 21.
and unballanced translocation of long arms of chromosome 14 and 21 (robertsonian translocation)
explain what the karyotype looks like in robersonian translocation
the individual has a translocation of chromosome 21 and 14 (the long arms). that translocation stays on the 14 but the individual has a replication of the normal chromosome 21 so they end up with three copies of chromosome 21
what effects does thalidomide have on a growing fetus?
when fetus is exposed at 24 or 36 days, long bone growth is absent
overview of signal transduction
ligand bind
causes dimerization of receptors
causes phosphorylation on the cytoplasmic end of the receptor
causes down stream effect.
molecules are activated that go into nucleus and affect transcription
who is the intermediary protein that promote TGF-B signalling?
Smads promote TGF-B signalling. When a ligand binds to TGF-B, it causes the receptor to dimerize. then causes it to phosphorylate Smads and the phosphrylated Smad binds to another and they travel into the nucleus and bind to DNA response element and regulate transcription
a deficit in Smads will cause an inhibition in the
TGF-B pathway
what role do proteoglycans play in FGF receptor binding?
FGF ligands are made as monomers but the receptors are dimerized. SO proteoglycans bind two ligands and present them to the receptor allowing it to bind and start the kinase cascade.
how do cells use reciprocal inhibition to split into inner cell mass and trophoectoderm and what stages does it happen?
there are two transcription factors available in all pluripotent cells. What happens in as the blastocyst is formed on day 7, some cells randomly inhibit one TF and start differentiating into different cells one for the ICM and the other for the trophoectoderm
when does the primitive streak form? where does this happen?
day 14. embrynic mesoderm and embryonic endoderm are derived from cells that enter primitice streak during gastrulation. this happens at the node
What is the TGF-B family of genes called and why?
TGF-b family of genes are expressed at the node( thus they are called nodal genes) their job is to initiate mesoderm formation
what happens of you knock out the nodal gene in mice?
you fail to produce the primitive streak thus there will be no mesoderm formation.
what role does nodal gene play even earlier than the primitive streak formation? what why is that structure important
it is involved in the formation of the anterior visceral endoderm. the anterior visceral endoderm (AVE) is required for head patterning. you dont get appropriate development of the head if the AVE doesnt develop
how does nodal make sure it is isolated to the only part of the cell that will develop into mesoderm?
after the AVE is formed, it makes antagonists that limit nodal expression anywhere else in the embryo to only the area that will form mesoderm
what is BMP4 and what does it do?
another member of the TGF-b family. it ocupies the whole blue area on the embryo and suppreses mesoderm formation and nervous system formation
how do you increase mesoderm formation with BMP4 out here limiting everything?
expression of nodal comes with expression of noggin and chordin. these peptides can diffuse away from the node and bind to BMP-4 all the blue areas and prevent its action
what is goosecoid?
expressed in the node. joins with the AVE and helps produce the transcription factors needed for head patterning
what is brachyury?
if knocked out the whole posterior (tail portion) of the mouse is missing.
how does FGF interact with nodal and what is the consequence?
FGF is expressed at the node. its interaction with nodal leads to nodal develpment on one side of the embryo and determines the sidedness of the embryo
how does FGF signalling help further inhibit BMP4 and where?
FGF promotes expression of noggin and chordin. Noggin and chordin inhibit BMP4 in the midline and allows the notochord to form
what is the phenotype in mice with high levels of retnoic acid?
you get teratogenic effects. mouse ends up with poor development of the dorsal end of the mouse
how does Retnoic acid cause a the phenotypic changes we see?
RA has inhibitory effects on FGF. RA gradually turns of FGF in the posterior end. Speficifically FGF8
hox expression
in order to turn on the posterior structures, you need longer exposure to FGF but if there is too much retnoic acid, FGF turns off before it is able to make the posterior structures.
