Neuron
Volume 50, Issue 6, 15 June 2006, Pages 841-853
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Article
FGF as a Target-Derived Chemoattractant for Developing Motor Axons Genetically Programmed by the LIM Code

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Summary

LIM transcription factors confer developing axons with specific navigational properties, but the downstream guidance receptors and ligands are not well defined. The dermomyotome, a transient structure from which axial muscles arise, is the source of a secreted long-range chemoattractant specific for medial-class spinal motor neuron axons (MMCm axons). We show that fibroblast growth factors (FGFs) produced by the dermomyotome selectively attract MMCm axons in vitro. FGF receptor 1 (FGFR1) expression is restricted to MMCm neurons, and conditional deletion of FGFR1 causes motor axon guidance defects. Furthermore, reprogramming the identity of limb-innervating motor neurons to that of dermomyotome-innervating MMCm cells using the LIM factor Lhx3 induces FGFR1 expression and shifts an increased number of motor axons to an FGF-responsive state. These results point to a role for FGF signaling in axon guidance and further unravel how downstream effectors of LIM codes direct wiring of the developing nervous system.

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Present address: Cellular and Molecular Neurobiology Laboratory, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.