Bcl11A/CTIP1 regulates expression of DCC and MAP1b in control of axon branching and dendrite outgrowth

Mol Cell Neurosci. 2009 Nov;42(3):195-207. doi: 10.1016/j.mcn.2009.07.006. Epub 2009 Jul 17.

Abstract

The extension of axon branches is important for target innervation but how axon branching is regulated is currently not well understood. Here, we report that Bcl11A/CTIP1/Evi9, a zinc finger transcription factor, downregulates axon branching. Knockdown of Bcl11A induced axon branching and multi-axon formation, as well as dendrite outgrowth. Due to alternative splicing, a single Bcl11A gene encodes two protein products, Bcl11A-L and -S. Bcl11A-L was found to be the main Bcl11A player in regulation of neurite arborization; Bcl11A-S is an antagonist of Bcl11A-L. Time-lapse study further suggests that Bcl11A-L knockdown enhances axon dynamics and increases the duration of axon outgrowth. Finally, the expression of DCC and MAP1b, two molecules involved in direction and branching of axon outgrowth, is controlled by Bcl11A-L. DCC overexpression rescues the phenotype induced by Bcl11A-L knockdown. In conclusion, this report provides the first evidence that Bcl11A is important for neurite arborization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Axons / ultrastructure
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • DCC Receptor
  • Dendrites / physiology*
  • Dendrites / ultrastructure
  • Gene Knockdown Techniques
  • Hippocampus / cytology
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Repressor Proteins
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • BCL11A protein, human
  • Carrier Proteins
  • DCC Receptor
  • Dcc protein, rat
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • microtubule-associated protein 1B