NEUS 609 - Axonal Growth & Guidance II

Rac, Cdc452

attractive cues activate __, and __ to promote elongation of microfilaments and engagement of the clutch proteins

• growth cone advance

Rho

repulsive cues activate ___ to promote severing of microfilaments and disengagement of the clutch proteins

• growth cone collapse and retraction 

asymmetric

___ expression of receptors for attractive and repulsive cues leads to growth cone turning

tyrosinated

dynamic microtubules are post-translationally ___

acylated, de-tyrosinated

stable microtubules are post-translationally ___ or ___

neural circuits

growth cone navigation establishes ____ such as the retinal connections

ipsilateral

same side of the brain, the axon does not decussate

contralateral

opposite side of the brain, the axons do decussate

resonance hypothesis

non-selective extension of axons to numerous targets, and only connections electrically active are kept

• Paul Weiss

• 1920s

• mismatched connections are eliminated

chemospecificity hypothesis

selective axonal growth guided by specific soluble factors and adhesive contacts to reach appropriate targets

• Roger Sperry

• 1940s

• Nobel prize in 1981

• mismatched connections are avoided

Cell-adhesion molecules

• cell-cell interactions

• includes N-cadherins, NCAM, fasciculin

• increase axon growth and fasciculation (roads)

attractive substrate adhesion molecules

• cell-extracellular matrix (ECM) interactions

• laminin (EMC molecule binding to integrin receptors on cell surface)

• fibronectin

• increase axon growth and fasciculation (roads)

repellant substrate adhesion molecules

• cell-extracellular matrix (ECM) interactions

• growth cone turning or collapsing (guard-rails)

• slits

• ephrin

repulsive diffusable guidance molecules

semaphorins

• soluble ones bind to neuropilin receptors to mediate repulsion

• membrane ones bind to plexin receptors to mediate defasciculation

attractive diffusable guidance molecules

netrins

• expressed by floor plate creating gradient

• bind to “frazzled” receptor

growth factors like BDNF

• binds to TrkB receptor

integrins

cell matrix adhesion proteins that are heterodimers consisting of alpha and beta subunits

• which molecule they bind to depends on subunit combination

• binds to laminin

• binds to adapter proteins that cross-link them to microfilaments

cadherin

cell-cell adhesion transmembrane proteins that dimerize at the cell surface

• bind to other __ dimers on opposite membrane

• calcium dependent binding (calcium binds to and make extracellular domain stiffen)

• cytoplasmic domain binds to beta-catenin and linkers proteins

ephrin

membrane bound proteins and associated receptor with bidirectional, mostly repulsive signaling

• ligand = ___

• receptor = Eph

• gradient in tectum to establish retinal circuitry

anterior

MORE Eph receptors expressed = more sensitivity to ephrin = stops early = ___ tectum

posterior

LESS Eph receptors expressed = less sensitive to ephrin = goes farther = __ tectum

chemotaxis

movement of motile cell or organism in a direction corresponding to an increase or decrease in concentration of a specific substance

netrin

soluble guidance molecule binding to both DCC and Unc-5H receptors, thus can have completely opposite effects.

DCC

when netrin binds to ___ receptors, it is an attractive cue.

cells expressing ___ are attracted by netrins

Unc-5H

when netrins bind to ___ receptors they are repulsive cues.

cells expressing ___ receptors are repelled by netrins.

robo

slits, substrate-bound repulsive cues, bind to the ___ receptor and regulate midline repulsion

• upregulation of ___ receptors expression AFTER crossing the midline ensures that the axons keep growing away from it