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Developmental

Lecture 15

QuestionAnswer
An enzyme linked receptor binds a dimer molecule forces the receptor to dimerize.
Each monomer then causes phosphorylation of the other (hence a kinase) at specific tyrosines and changes conformation of enzyme.
These phosphorylated tyrosines then bind certain intra cellular signaling proteins and the signal is transduced.
A subclass of RTK are the ephrin receptors
Ephrin ligands are tethered or integral proteins and bind ephrin receptors on another cell, therefore cell-cell connections form (at least transiently). Plays role in nervous system patterning.
cKit and Mgf are involved in directional migration of PGC’s, melanoblasts and erythropoietic stem cells
PGC’s set aside early and migrate to the genital ridge and the gonads. In many instances over long distances or via the circulatory system or from yolk sac’s etc.
In mice ____ ____ codes for cKit (type of RTK) and is expressed by PGC’s. cKit’s ligand is Mgf and is encoded by the steel gene. W gene
If either W or steel is mutated get sterility, anemia and pigment color change (deficiencies in PGC migration, melanoblast migration from the NC and hematopoiesis) ...
The ephrin (bond to cell) (RTK) Ephreceptor system is important for NC migration.
Receptor ___ is present on anterior somites and on NC cells. EphB3
Nerve growth is due to both growth cone formation influenced by actin microfilaments and elongation due to microtubules.
The advancing tip is called the growth cone.
. Extending from the surface of the growth cone are fine protrusive strands called filopodia (thread like feet) or broad region called lamellipodia (plate like feet)).
filopodia and lamellipodia contain microfilaments.
Microtubules are in the center of the growth cone and extend to the soma – Very dynamic processes for both microfilament and microtubule.
Growth path is determined by extending and retracting filopodia. If attach the nerve axon (neurite) advances.
In order for nerve growth to occur need both microfilaments and microtubules
No microfilaments (cytochalasin) the growth cone become nonfunctional No filopodia form and therefore can’t adhere to the substrate and extend.
The extension it has achieved is intact because of microtubules.
Meanwhile with ____ the MT is inhibited and the axon collapses; however exploration still occurs. cholchicine
Stereotaxis Growth cone “feels” the physical surroundings and follows specific pathway – Found to occur in grooves in tissue culture plates.
Contact inhibition Growth cone extends until it comes in contact with another migrating cell. It stops and proceeds in another direction.
Haptotaxis Growth cone follows a path of greatest adhesive strength, up to a point.
Chemotaxis Local chemicals attract or repel the growth cone
Future ventral spinal chord releases netrin I and 2 - Chemotaxis Netrin 1 – Floorplate Netrin 2 – ventral but not floor plate
AER formed due to signals from lateral plate mesoderm
Signals are probably BMP’s
Signal from AER to stimulate bud outgrowth includes fibroblast growth factors (FGF’s). Increases mitosis and mesodermal cell immigration
Epithelium is separated from mesenchyme by the basal lamina
The AER is formed due to signals from the lateral plate mesoderm (epidermal-mesenchyme interaction). These signals may be BMP’s.
Removal of AER stimulates death of underlying mesenchyme and stops forward progression.
The signal from AER to stimulate bud growth includes FGF’s probably increase mitosis and possibly immigration of mesodermal cells from surrounding areas
Lung Development – among the last of mammalian organs to fully differentiate
Lung forms by budding and branching which is typical of many internal organs.
Thoracic mesenchyme allows for branching
Neck mesenchyme doesn’t get trachea.
The tips of the epithelial branches are highly mitotic and therefore ligands that stimulate mitosis should stimulate bud growth and branching.
influence branching of lung epithelium. Transforming growth factor Beta (TGF-Beta) epidermal growth factor (EGF) and some FGF
TGF-Beta lowers bud growth and branching if inactivate its receptor on the epithelium get increase in bud growth and branching.
FGF 10 stimulates lung endodermal epithelium to undergo branching and is localized in the mesenchyme at the tips of the buds. Homozygous FGF2 receptor mutants have abnormal lungs and severely reduced bronchial branching.
Salivary Glands Tips of buds  increase mitotic activity  buds lengthen to become tubules of branching networks between the buds and tubules have lots of collagen which stabilizes.
Cleft formation is initiated at tip due to micro filaments and a weakening of the basal lamina by enzymes.
Wolffian duct elongates forming ureteric bud.
The ureteric buds branch due to mesenchymal cell aggregation. Renal vesicle from.
. Branching and aggregation continue get differentiation into nephrons and glomeruli.
The mesenchyme near the Wolffian duct secretes secretes GDNF (glial derived neurotrophic growth factor) – named because first discovered for Nervous system.
GDNF activates cRET receptor (a RTK type receptor) on the Wolffian duct (No cRET no ureter).
Gastrula Development – Amphibian  blastula forms, Get bottle cell formation at region of blastopore and get involution through blastopore.
1st mesoderm begins to involute and then adjacent cells change shape to bottle cells and we get convergent extension to further drive involution.
Apical constriction of the bottle cells cause their shape change and initiate involution.
Transplanting noninvoluting marginal zone cells to a region that normally involutes they do not involute. They retain the behavior they had from their previous location.
Conversely, if you take cells from region of involution and place them in a noninvoluting area they attempt convergent extension.
Created by: AshCha
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