Dual roles of Akirin2 protein during Xenopus neural development

J Biol Chem. 2017 Apr 7;292(14):5676-5684. doi: 10.1074/jbc.M117.777110. Epub 2017 Feb 13.

Abstract

To ensure correct spatial and temporal patterning, embryos must maintain pluripotent cell populations and control when cells undergo commitment. The newly identified nucleoprotein Akirin has been shown to modulate the innate immune response through epigenetic regulation and to play important roles in other physiological processes, but its role in neural development remains unknown. Here we show that Akirin2 is required for neural development in Xenopus and that knockdown of Akirin2 expands the expression of the neural progenitor marker Sox2 and inhibits expression of the differentiated neuronal marker N-tubulin. Akirin2 acts antagonistically to Geminin, thus regulating Sox2 expression, and maintains the neural precursor state by participating in the Brg1/Brm-associated factor (BAF) complex mediated by BAF53a. Additionally, Akirin2 also modulates N-tubulin expression by acting upstream of neuronal differentiation 1 (NeuroD) and in parallel with neurogenin-related 1 (Ngnr1) during terminal neuronal differentiation. Thus, our results reveal a novel model in which Akirin2 precisely coordinates and temporally controls Xenopus neural development.

Keywords: Xenopus; cell differentiation; chromatin remodeling; embryo; neurodevelopment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / physiology*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Geminin / genetics
  • Geminin / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Chromosomal Proteins, Non-Histone
  • Geminin
  • Nerve Tissue Proteins
  • Repressor Proteins
  • SOXB1 Transcription Factors
  • Xenopus Proteins
  • neurogenin, Xenopus