Growth cones detect extracellular signals and guide axons to their targets.

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Presentation transcript:

Growth cones detect extracellular signals and guide axons to their targets

Membrane signals and topography

Flanagan and O’Leary Cell (1996) Elf-1 (ephrinA2) repels anterior (nasal) axons

Ephrins and topographic patterning

Axon guidance at the midline

Trajectory of commisural axons

A floorplate chemoattractant guides commisural axons (Tessier-Lavigne and Jessell)

Netrin expression in the spinal cord (Serafini and Tessier-Lavigne)

Netrin expressed in COS cells attracts commisural axons (Serafini and Tessier-Lavigne)

Ventral spinal cord inhibits NGF-dependent sensory axons (Kolodkin and Goodman)

Sema 3A expressed in COS cells inhibits NGF-dependent sensory axons (Kolodkin and Goodman)

Oriented apical dendrite outgrowth Non-oriented apical dendrite outgrowth E15 embryos Transgenic mice expressing GFP under  -actin promoter The slice overlay assay: a new technique to study apical dendrite patterning. Early postnatal cortical slices Polleux and Ghosh

Sema3A is expressed at high levels in the cortical plate during neuronal differentiation Modified from Giger et al. J. Comp. Neurol., 375, (1996). VZ SVZ SP IZ 6a CP MZ

Guidance of cortical axons by extracellular signals (Polleux and Ghosh)

Sema3A repels cortical axons

Pyramidal neuron morphology in Sema3A null mice

Sema3A is an attractant for cortical dendrites

Soluble Guanylate Cyclase co-localizes with MAP2 in the emerging apical dendrite

DMSOODQ P3 slice E15 GFP cells 4 div Inhibition of soluble Guanylate Cyclase and PKG disrupts apical dendrite orientation Rp-8-pCPT-cGMPS SQ Rp-cAMPS 150 microns

Guanylate Cyclase Confers Distinct Responses to Axons and Dendrites Sema 3A Guanylate Cyclase

A-P guidance in the spinal cord

A-P guidance requires a diffusible signal (Zou and Tessier-Lavigne)

Role of Wnts in A-P guidance

Frizzled-3 is required for A-P guidance

Topographic projections from retina to tectum

Ephrins are expressed in a posterior-anterior gradient in the tectum (Flanagan, Bohnoeffer)