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Axon and Dendritic Branching

Axon and dendritic branching occur simultaneously in the developing brain-Once at their target, presynaptic retinal axons branch and make contact with postsynaptic tectal

neurons

-Neurons transfected with GFP in live Xenopus tadpoles

Common axon branching processes in the vertebrate nervous system

-Arborization usually occurs in axons that have arrived at their final target. Arborization reach

final target.-Bifurcation occurs when axons split to project to two targets in opposite directions (ie sensory

neurons) Bifurcation splits to two different targets.

-Collateral formation establishes contacts with multiple targets (ie layer 5 cortical neurons)

Collateral formation establishes contact with multiple targets.

Mechanisms that specify the location of axon branching

-Branching at axon terminals-Local induction

-Local inhibition coupled with global promotion

Changes in the actin and microtubule cytoskeleton also lead to axon branching-Pausing growth cone, developing branch, elongating branch

Sensory axon branching in the spinal cordSchematized cross-sections of the vertebrate developing spinal cord illustrate three branching

forms of dorsal root ganglion (DRG) sensory axons

-The DRG flanks the spinal cord and contains the cell bodies of sensory neurons that initially

generate a peripheral axon that projects to the skin or muscle, and a central axon that projectscentrally to the spinal cord

-The central axons of DRG neurons bifurcate once they reach the dorsal root entry zone (DREZ;

green stripe) of the spinal cord and continue to extend in opposite directions along the anterior-posterior (A-P) axis

An illustration of sensory axon bifurcation-An axon of a DRG neuron bifurcates at the DREZ of the spinal cord. The two resulting branches

(blue) extend in opposite directions along the anterior-posterior (A-P) axis, perpendicular to the

primary axon (red). Summary of bifurication defects in mouse mutants that lack C-tpe natricuteri

peptide (CNP) or with impaired SLIT signaling (Slit1, Slit2 or Robo1, Robo2, double mutants).C) Model of axon bifurication based on observations of defects in mutant mice.

Axon targeting and collateral branch formation

-Layer 5 neurons in motor and visual cortices send long projecting axons towards the spinal cordThese axons send collateral branches to intermediate targets. Collteral branches are retained and

some are eliminated. Neurons from motorcortex eliminated branches from uperior colliculis and

layer 5 neurons from visual cortex selectively eliminate collaterals projecting to the spinal cord.Semaphorins play a role in collateral branch elimination

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Axon arborization at the target

BDNF and Nectrin-1 modulate RGC axon arborization at the target

BDNF and its receptor TrkB affect multiple aspects of neuronal development and function

including axon branching

Manipulate BDNF levels in the optic tectum (increase BDNF or decrease by blocking antibodies

to BDNF)

BDNF increases the dynamic branching of retinal axons at the target

If BDNF function is blocked with antibodies that prevent binding to its receptor, then retinal

axons prune back

Mechanisms underlying activity-dependent regulation of axon branching

-Axon branching is a dynamic process that involved branch addition and branch retraction.Branching dynamic can be modulated by neural activity

-Neighboring axonal branches compete for innervation territory in the targer structure. Typically

the axon experiencing the greatest amount of activity wins the competition by inhibiting the

arborization of neighboring axons-Axon branching is tightly coupled to synapse development. New synapses preferentially form

on new branches, and new branches preferentially form near mature synapses.

Multiple factors collaborate to control axon branching at the target

-BDNF a branching signal collaborates with EphrinA-EphA signaling to specify axon branching

within a specific termination zone along a target

Dendritic differentiation

Golgi impregnation method used to visualize neurons and spines in vivo

Early differentiation of neurites

Advantage of culture systems to study dendritic differentiation-In tissue culture, neurons begin putting out several minor processes that seem basically

equivalent. One of these will differentiate into an axon as it extends, and the shorter ones

differentiate into dendrties.

Extracellular signals and dendritic growth and branching

-Sema3A

-Notch

-Slit-Neurotrophic factors

Dendritic orientation is guided by ligand-receptor interactions

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-Artificially inverting a gradient of Sema3 results in neurons with dendrites projecting in the

opposite direction in the cortex

Evidence obtained in slice preparation

-Normal dendritogenesis