RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex

Cell Rep. 2013 Feb 21;3(2):458-71. doi: 10.1016/j.celrep.2013.01.012. Epub 2013 Feb 7.

Abstract

Accumulating evidence suggests that many brain diseases are associated with defects in neuronal migration, suggesting that this step of neurogenesis is critical for brain organization. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here, we identified the zinc-finger transcriptional repressor RP58 as a key regulator of neuronal migration via multipolar-to-bipolar transition. RP58(-/-) neurons exhibited severe defects in the formation of leading processes and never shifted to the locomotion mode. Cre-mediated deletion of RP58 using in utero electroporation in RP58(flox/flox) mice revealed that RP58 functions in cell-autonomous multipolar-to-bipolar transition, independent of cell-cycle exit. Finally, we found that RP58 represses Ngn2 transcription to regulate the Ngn2-Rnd2 pathway; Ngn2 knockdown rescued migration defects of the RP58(-/-) neurons. Our findings highlight the critical role of RP58 in multipolar-to-bipolar transition via suppression of the Ngn2-Rnd2 pathway in the developing cerebral cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Movement
  • Cells, Cultured
  • Cerebral Cortex / growth & development*
  • Embryo, Mammalian / metabolism
  • Embryonic Development
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis
  • Neurons / cytology
  • Neurons / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins
  • Neurog2 protein, mouse
  • RNA, Small Interfering
  • Repressor Proteins
  • Zbtb18 protein, mouse