LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions

Cell. 2002 Jul 26;110(2):237-49. doi: 10.1016/s0092-8674(02)00823-1.


LIM homeodomain codes regulate the development of many cell types, though it is poorly understood how these factors control gene expression in a cell-specific manner. Lhx3 is involved in the generation of two adjacent, but distinct, cell types for locomotion, motor neurons and V2 interneurons. Using in vivo function and protein interaction assays, we found that Lhx3 binds directly to the LIM cofactor NLI to trigger V2 interneuron differentiation. In motor neurons, however, Isl1 is available to compete for binding to NLI, displacing Lhx3 to a high-affinity binding site on the C-terminal region of Isl1 and thereby transforming Lhx3 from an interneuron-promoting factor to a motor neuron-promoting factor. This switching mechanism enables specific LIM complexes to form in each cell type and ensures that neuronal fates are tightly segregated.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Interneurons / metabolism
  • Interneurons / physiology*
  • LIM Domain Proteins
  • LIM-Homeodomain Proteins
  • Mice
  • Motor Neurons / metabolism
  • Motor Neurons / physiology*
  • Protein Binding
  • Rats
  • Transcription Factors


  • DNA-Binding Proteins
  • Homeodomain Proteins
  • LIM Domain Proteins
  • LIM-Homeodomain Proteins
  • Ldb1 protein, mouse
  • Lhx3 protein
  • Transcription Factors