The epigenetic factor Kmt2a/Mll1 regulates neural progenitor proliferation and neuronal and glial differentiation

Yin Cheng Huang, Hung Yu Shih, Sheng Jia Lin, Ching Chi Chiu, Tsu Lin Ma, Tu Hsueh Yeh, Yi Chuan Cheng

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Multiple epigenetic factors play a critical role in cell proliferation and differentiation. However, their function in embryogenesis, especially in neural development, is currently unclear. The Trithorax group (TrxG) homolog KMT2A (MLL1) is an important epigenetic regulator during development and has an especially well-defined role in hematopoiesis. Translocation and aberrant expression of KMT2A is often observed in many tumors, indicating its proto-oncogenic character. Here, we show that Kmt2a was essential for neural development in zebrafish embryos. Disrupting the expression of Kmt2a using morpholino antisense oligonucleotides and a dominant-negative variant resulted in neurogenic phenotypes, including downregulated proliferation of neural progenitors, premature differentiation of neurons, and impaired gliogenesis. This study therefore revealed a novel function of Kmt2a in cell proliferation and differentiation, providing further insight into the function of TrxG proteins in neural development and brain tumors.

Original languageEnglish
Pages (from-to)452-462
Number of pages11
JournalDevelopmental Neurobiology
Volume75
Issue number5
DOIs
Publication statusPublished - May 1 2015
Externally publishedYes

Keywords

  • Differentiation
  • Kmt2a
  • Neural progenitors
  • Proliferation
  • Zebrafish

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Medicine(all)

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