cell migration

Question 1

How is cell migration or guidance controlled?

Answer 1

Cell guidance is controlled by attractive and repulsive extracellular guidance cues

Question 2

what Can extracellular cues be?

Answer 2

on surface of receptors.
Diffusible factors secreted by proximal or distant cells
Substrate-bound factors which are components of the extracellular matrix. (integrins)

Question 3

what are Integrins

Answer 3

transmembrane proteins which bind to the actin filaments on the cytosolic side of the plasma membrane and to adhesive molecules of the extracellular matrix (e.g. fibronectin and laminin) on the non-cytosolic side to anchor the protusions to the surface

Question 4

what are Netrins

Answer 4

diffusible proteins that mediate both attraction and repulsion

Question 5

Eph Receptors

Answer 5

Membrane tyrosine kinase receptors (13 in humans)
Juxtacrine (contact-dependent) signaling mechanism
Ephrin receptor binds ligand as heterodimer which then associates with another heterodimer to form a tetramer (not shown)
Extracellular side contains: Globular domain that binds the ligand, Cysteine rich region, 2 fibronectin repeats
Transmembrane region: single pass
Cytoplasmic Region contains: juxtamembrane domain with 2 conserved tyrosines, a tyrosine kinase domain, sterile a motif (SAM), PDZ binding motif

Question 6

Eph

Answer 6

Large family: at least 8 in humans
Ligand is membrane bound
Two kinds: Ephrin A contains a GPI anchor and Ephrin B contains a polypeptide membrane spanning segment and is synthesized in the ER.
Both Ephrin A and B can trigger reverse signaling “into” the ephrin expressing cell (bidirectional signaling)

Question 7

retinotectal system

Answer 7

1. Retinal neurons map to the tectum of the midbrain.
2. Axons from the nasal retina (the side closest to the nose) project to the posterior tectum, and axons from the temporal retina (the side farthest from the nose) project to the anterior tectum, with intermediate regions of retina projecting to intermediate regions of tectum.

Question 8

Guidance cues act cooperatively

Answer 8

Axons sometimes need to migrate over very long distances to reach their targets.

Requires the coordination of multiple guidance systems expressed at discrete positions along the route of a migrating axons (Fig 10.33).

Repelled from retinal periphery by chondroitin sulfate A
Axons enter the optic disc via a Netrin-DCC interaction
Slit-Robo repulsion keeps the axon in the optic tract (zones of inhibition).

EphB1 expressing axons are kept on one side by being repelled by Ephrin-B2

Question 9

SLIT

Answer 9

chemorepulsive dorsal cue.
it is secreted by the neural cells in the midline acts to prevent most neurons from crossing the midline from either side

Question 10

Robo

Answer 10

Roundabout protein.
receptor for slit.
downregulate robo to cross midline. after crossing re-express it.

Question 11

Slit/Robo system

Answer 11

system cooperate with netrin/DCC system to permit the commissural neurons to cross the midline

Question 12

posterior

Answer 12

WNTS