Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors

Neuron. 2003 Jun 5;38(5):731-45. doi: 10.1016/s0896-6273(03)00296-4.


Inductive signaling leads to the coactivation of regulatory pathways for specifying general neuronal traits in parallel with instructions for neuronal subtype specification. Nevertheless, the mechanisms that ensure that these pathways are synchronized have not been defined. To address this, we examined how bHLH proteins Ngn2 and NeuroM controlling neurogenesis functionally converge with LIM-homeodomain (LIM-HD) factors Isl1 and Lhx3 involved in motor neuron subtype specification. We found that Ngn2 and NeuroM transcriptionally synergize with Isl1 and Lhx3 to specify motor neurons in the embryonic spinal cord and in P19 stem cells. The mechanism underlying this cooperativity is based on interactions that directly couple the activity of the bHLH and LIM-HD proteins, mediated by the adaptor protein NLI. This functional link acts to synchronize neuronal subtype specification with neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Avian Proteins*
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Chick Embryo
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Helix-Loop-Helix Motifs / genetics*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • LIM Domain Proteins
  • LIM-Homeodomain Proteins
  • Mice
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Spinal Cord / cytology
  • Spinal Cord / embryology*
  • Spinal Cord / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Avian Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • LIM Domain Proteins
  • LIM-Homeodomain Proteins
  • Ldb1 protein, mouse
  • Lhx3 protein
  • Nerve Tissue Proteins
  • NeuroM protein, chicken
  • Neurog2 protein, mouse
  • Neuropeptides
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1