Foxp1 and lhx1 coordinate motor neuron migration with axon trajectory choice by gating Reelin signalling

PLoS Biol. 2010 Aug 10;8(8):e1000446. doi: 10.1371/journal.pbio.1000446.

Abstract

Topographic neuronal maps arise as a consequence of axon trajectory choice correlated with the localisation of neuronal soma, but the identity of the pathways coordinating these processes is unknown. We addressed this question in the context of the myotopic map formed by limb muscles innervated by spinal lateral motor column (LMC) motor axons where the Eph receptor signals specifying growth cone trajectory are restricted by Foxp1 and Lhx1 transcription factors. We show that the localisation of LMC neuron cell bodies can be dissociated from axon trajectory choice by either the loss or gain of function of the Reelin signalling pathway. The response of LMC motor neurons to Reelin is gated by Foxp1- and Lhx1-mediated regulation of expression of the critical Reelin signalling intermediate Dab1. Together, these observations point to identical transcription factors that control motor axon guidance and soma migration and reveal the molecular hierarchy of myotopic organisation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axons / metabolism
  • Axons / physiology*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Extremities / innervation
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Developmental
  • Growth Cones / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • LIM-Homeodomain Proteins
  • Motor Neurons / metabolism
  • Motor Neurons / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Signal Transduction*
  • Spinal Cord / metabolism
  • Transcription Factors

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Forkhead Transcription Factors
  • Foxp1 protein, mouse
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lhx1 protein, mouse
  • Nerve Tissue Proteins
  • Repressor Proteins
  • Transcription Factors
  • Serine Endopeptidases
  • reelin protein