Chapter 4 Flashcards
What are cadherins?
Transmembrane proteins critical for segregation of cell types in the embryo.
How do cadherins control epithelial cells?
Epithelial cells are sorted by the type of cadherin proteins present in their cell membranes. Epithelial cells undergo EMT when E-cadherin gene expression is repressed.
Define the differences between juxtacrine, paracrine, and endocrine signalling.
Juxtacrine: Need to touch the target cell
Paracrine: Signalling proteins travel across gap between cells
Endocrine: Secreted signaling proteins are secreted into the bloodstream until they reach their target cells/tissues
How do E-cadherins, catenins, and actin work to bind cells together?
The five cadherin subunits (important: EC1 adhesive recog site, EC2 binds calcium) bind to catenins which are bound to actins inside the cell. One EC1 site can bind to another EC1 site and link two cells together.
Define induction.
The process by which one cell’s population influences the development of neighboring cells via interactions at a close range (juxta or para).
What is competence.
A cell population’s ability to respond to induction.
In lens development, what gene expression is required for a cell to be competent and thus induced to form the lens in mammals?
BMP4 expression: Sox2/3 transcription
FGF8 expression: L-Maf transcription
Pax 6 receptor expression and for FGF8 and BMP4 needed.
Are all inducer factors morphogens all of the time?
No. Not all inducer factors are morphogens and those that are in some cases are not acting as morphogens all the time. Induction can also occur through juxtacrine signalling.
What is a typical signalling pathway?
A receptor that can dimerize on contact with a ligand and self-phosphorylates, then acting as a kinase to phosphorylate a responding protein.
Name the steps in the RTK pathway.
- FGF binds to FGF receptor extracellularly, dimerizes into RTK in the membrane
- RTKs autophosphorylate, recruit GEF + GAP
- GEF + GAP act to phosphorylate Ras
- Ras activates Raf which phosphorylates MEK
- MEK phorphorylates ERK in the nucleus
- ERK phosphorylates the transcription factor which activates it and allows binding + transcription
Name the steps in the JAK-STAT pathway. What kind of signalling pathway is this?
- Prolactin (or FGF) binds
- Receptors dimerize
- JAKS autophosphorylate
- JAKs phosphorylate Stat5
- Stat5 dimerizes
- Stat5 dimer enters nucleus, regulates transcription
Classic RTK pathway.
What can a GOF mutaation in FgfR3 cause?
Dwarfism, kinase is activates too soon and produces too little cartilage b/c FGF through FGFR3 inhibits chondrocyte production, smaller bones if heterozygous (Achondroplasia), lethal if homozygous (thanatophoric dysplasia). A mutant receptor can be on all the time.
Name the key components of the hedgehog pathway.
Patched and smoothened form a complex, patched inhibits smoothened in the absence of hedgehog.
PKA is able to phosphorylate and cleave Ci, the cleaved halves migrate to the nucleus, no transcription occurs as the cleaved half blocks transcription.
In the presence of hedgehog, patched is inhibited and smoothened inhibits PKA and Slimb, Ci is freed uncleaved, migrates to nucleus and activates transcription.
Ci is Cubitus Interruptus, vertebrate homologs are GLI 1-3 proteins.
What is the main difference for the Hedgehog pathway in vertebrates?
The presence of primary cilium.
What can SHH inhibition cause?
Cyclopia. Development of embryo without a spinal column because SHH from the notochord is crucial to induce somites to form vertebrae.
