Molecular Pattern Formation Flashcards
Trisomy 13 phenotype:
- midline defects
- Cleft lip, palate
- holoprosencephaly (single ventricle)
Trisomy 18 phenotype:
- Intrauterine growth restriction
- Clenched hands
- Low set ears
Mutations in specific transcription factors can cause developmental disorders in:
- overall body patterning or genesis of specific organs
How many gene deficits are sufficient to interrupt specific organ development?
one (single gene deficit)
A teratogen is:
- an agent which can cause a birth defect.
- It is usually something in the environment that the mother may be exposed to during her pregnancy.
When do teratogens act?
- during critical times of organ formation.
Most major birth defects arise from genetic or environmental abnormalities during what time period of gestation?
the first two months
What weeks of pregnancy is the embryo not susceptible to teratogens?
- first two weeks; “pre-differentiation” phase.
- embryo will recover cells damaged or killed.
Risks of birth defects from many teratogens are highest when?
- in the embryonic period
- 3-8 weeks in humans
Transforming growth factor beta (TGF-b) binds to what kind of receptors?
serine-threonine kinase receptors
Fibroblast growth factor (FGF) binds to what kind of receptors?
tyrosine kinase receptors
Steps in TGF-beta signaling pathway:
- TGF-beta ligands bind as dimers to a ser/thr kinase type II receptor.
- type II ser/thr kinase receptor dimerizes with and phosphorylates a type I ser/thr kinase receptor.
- phosphorylated type I ser/thr kinase receptor phosphorylates folded Smad2/3.
- Phosphorylated Smad2/3 unfolds and dimerizes with Smad4.
- Smad2/3-Smad4 dimer migrates to nucleus to alter gene expression.
Antagonists of TGF-beta peptides can regulate TGF-beta activity via:
- binding TGF-b receptors
- preventing formation of active TGF-beta ligand dimers
Steps in FGF-Heparan Sulfate signaling pathway:
- FGF monomers bind to heparan sulfate side chains of a transmembrane protein
- heparan sulfate transmembrane protein presents FGF monomers to tyrosine kinase receptors, activating the signaling pathway
- presents FGF monomers in a dimer-like fashion
What is this image showing?
- Two TFs are required for two early embryonic lineages are initially coexpressed but expression becomes gradually restricted (via reciprocal inhibition) even before trophoblast and inner cell mass cells become completely sorted.
- Changes in molecular identity of cells occur prior to organization of specific cell types in early embryonic regions.
Process of gastrulation:
- Endodermal cells arise from the epiblast and enter the embryo via the primitive node and replace the hypoblast.
- Mesodermal cells arise from the epiblast and enter the embryo via the primitive node and spread.
What is the is area of active invagination into the inner embryo during gastrulation?
the primitive node
A mutation in a gene encoding for what protein will prevent formation of the primitive streak and production of the mesoderm?
- “nodal” protein
- a TGF-beta related peptide
What TGF-beta peptide is the major determinant of mesoderm formation?
nodal
“Nodal” protein expression is necessary for the development of what three embryonic structures?
-
anterior visceral endoderm (AVE)
- required for differentiation of anterior structures (head, brain, etc.)
- mesoderm
- primitive streak
Mesoderm gives rise to:
- most connective tissue
- induces nervous system formation from overlying ectoderm
After “nodal” protein induces formation of the anterior visceral endoderm (AVE), what does AVE do?
- produces inhibitors that suppress “nodal” protein expression in most of the embryo except for a small portion.
- This small portion is where the mesoderm and the primitive streak forms.
BMP4 in the human embryo:
- inhibits “nodal” protein
- suppresses mesoderm and nervous system formation
- promotes epidermis formation
BMP-4 is what kind of peptide?
TGF-Beta
