E(spl): genetic, developmental, and evolutionary aspects of a group of invertebrate Hes proteins with close ties to Notch signaling

Curr Top Dev Biol. 2014:110:217-62. doi: 10.1016/B978-0-12-405943-6.00006-3.

Abstract

Enhancer-of-split (E(spl)) was genetically characterized in Drosophila as a dominant mutation that interacts with an allele of Notch, the receptor in a multipurpose signaling pathway throughout development. Although dominant mutations are often not informative of the normal gene function, E(spl) turned out to encode a family of seven paralogous basic helix-loop-helix proteins of utmost importance in the implementation of the Notch signal in the receiving cell. They are transcriptionally induced by Notch in almost every instance where the signal is deployed, and they participate in numerous feedback circuits, where they interface with a panoply of additional more tissue-specific Notch targets to ensure the proper signaling outcome. Besides the bHLH domain, E(spl) contain a characteristic Orange domain and are classified in the Hes (hairy and enhancer-of-split) branch of the bHLH-Orange proteins. They act as DNA-binding repressors in close collaboration with the corepressor Groucho. In this review, we will focus on the regulation of E(spl) expression and on the function of E(spl) proteins. In the latter section, we will present some of the best-studied developmental events where E(spl) function has been analysed as well as the molecular mechanism of E(spl) activity that has transpired. Finally, we will review the evolution of this protein family, which, albeit of relatively recent origin, present only in insects and crustaceans, has undergone extensive diversification, including gene loss and duplication. Importantly, many of the characteristics of E(spl) proteins are more deeply rooted in the very ancient larger bHLH-O family, which seems to have forged a connection with the Notch pathway from the very beginning of multicellular animal life.

Keywords: Drosophila; Hes; Notch signaling; Notch targets; bHLH-Orange.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Central Nervous System / embryology
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Embryo, Nonmammalian
  • Evolution, Molecular
  • Gene Expression Regulation*
  • Invertebrates / genetics
  • Invertebrates / metabolism*
  • Neurons / cytology
  • Neurons / physiology
  • Receptors, Notch / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Drosophila Proteins
  • E(spl)m7-HLH protein, Drosophila
  • Receptors, Notch
  • Repressor Proteins