Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmitotic Neurons

Cell Rep. 2016 Apr 12;15(2):386-97. doi: 10.1016/j.celrep.2016.03.034. Epub 2016 Mar 31.

Abstract

Proneural proteins of the class I/II basic-helix-loop-helix (bHLH) family are highly conserved transcription factors. Class I bHLH proteins are expressed in a broad number of tissues during development, whereas class II bHLH protein expression is more tissue restricted. Our understanding of the function of class I/II bHLH transcription factors in both invertebrate and vertebrate neurobiology is largely focused on their function as regulators of neurogenesis. Here, we show that the class I bHLH proteins Daughterless and Tcf4 are expressed in postmitotic neurons in Drosophila melanogaster and mice, respectively, where they function to restrict neurite branching and synapse formation. Our data indicate that Daughterless performs this function in part by restricting the expression of the cell adhesion molecule Neurexin. This suggests a role for these proteins outside of their established roles in neurogenesis.

Keywords: NMJ; Pitt-Hopkins; TCF4; bHLH; daughterless; proneural; schizophrenia.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism
  • Basic Helix-Loop-Helix Proteins / metabolism*
  • Behavior, Animal
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Differentiation
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism*
  • Gene Knockdown Techniques
  • Mice
  • Mitosis*
  • Motor Activity
  • Neurites / metabolism*
  • Neuromuscular Junction / metabolism
  • Phenotype
  • Presynaptic Terminals / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Multimerization
  • Synapses / metabolism*
  • Synaptic Transmission
  • Transcription, Genetic

Substances

  • Basic Helix-Loop-Helix Proteins
  • Cell Adhesion Molecules, Neuronal
  • Drosophila Proteins
  • Da protein, Drosophila
  • Nrx protein, Drosophila
  • Tcf4 protein, Drosophila