A regulatory network to segregate the identity of neuronal subtypes

Dev Cell. 2008 Jun;14(6):877-89. doi: 10.1016/j.devcel.2008.03.021.


Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Axons / physiology
  • Chick Embryo
  • Electroporation
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Expression Regulation, Developmental / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • Interneurons / classification
  • Interneurons / cytology
  • Interneurons / physiology*
  • LIM Domain Proteins
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Biological
  • Motor Neurons / cytology
  • Motor Neurons / physiology*
  • Neurons / classification
  • Neurons / cytology
  • Neurons / physiology*
  • Response Elements / genetics
  • SELEX Aptamer Technique
  • Spinal Cord / cytology
  • Spinal Cord / embryology*
  • Spinal Cord / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Adaptor Proteins, Signal Transducing
  • Homeodomain Proteins
  • LIM Domain Proteins
  • Lmo4 protein, mouse
  • Transcription Factors
  • Vsx2 protein, mouse
  • Hb9 protein, mouse