The function of hairy-related bHLH repressor proteins in cell fate decisions

Bioessays. 1998 Apr;20(4):298-306. doi: 10.1002/(SICI)1521-1878(199804)20:4<298::AID-BIES6>3.0.CO;2-M.


Hairy-related proteins are a distinct subfamily of basic helix-loop-helix (bHLH) proteins that generally function as DNA-binding transcriptional repressors. These proteins act in opposition to bHLH transcriptional activator proteins such as the proneural and myogenic proteins; together, the activator and repressor genes that encode these proteins have co-evolved as a regulatory gene "cassette" or "module" for controlling cell fate decisions. In the development of the Drosophila peripheral nervous system, Hairy-related genes function at multiple steps during neurogenesis, for example, as positional information genes that establish the "prepattern" that controls where "proneural cluster" equivalence groups will form, and later as nuclear effectors of the Notch signaling pathway to "single out" individual precursor cells within the equivalence group. Hairy-related genes also function in the establishment and restriction of other types of equivalence groups, such as those for muscle and Malphigian tubule precursors. This general function in cell fate specification has been conserved from Drosophila to vertebrates and has implications for human disease pathogenesis.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation / genetics
  • DNA-Binding Proteins / physiology
  • Drosophila Proteins*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / physiology*
  • Female
  • Gene Expression Regulation*
  • Helix-Loop-Helix Motifs / physiology*
  • Humans
  • Insect Proteins / physiology*
  • Male
  • Membrane Proteins / physiology
  • Morphogenesis / genetics
  • Neurons, Afferent / physiology
  • Peripheral Nerves / cytology*
  • Peripheral Nerves / embryology
  • Peripheral Nerves / growth & development
  • Receptors, Notch
  • Repressor Proteins / physiology*
  • Sense Organs / embryology
  • Sense Organs / growth & development
  • Sense Organs / innervation
  • Species Specificity
  • Transcription Factors / physiology
  • Transcription, Genetic*
  • Transcriptional Activation
  • Vertebrates / embryology
  • Vertebrates / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • E(spl)mdelta-HLH protein, Drosophila
  • Insect Proteins
  • Membrane Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • Repressor Proteins
  • Transcription Factors
  • ac protein, Drosophila
  • gro protein, Drosophila