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 cord Schematized 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 projects centrally 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 anteriorposterior (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 cord These 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

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

-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