Journal
DEVELOPMENTAL NEUROBIOLOGY
Volume 75, Issue 5, Pages 452-462Publisher
WILEY-BLACKWELL
DOI: 10.1002/dneu.22235
Keywords
Kmt2a; neural progenitors; proliferation; differentiation; zebrafish
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Funding
- Chang Gung Memorial Hospital [CMRPD3B0041, CMRPD3B0042]
- National Science Council of Taiwan [102-2311-B-182-002-MY3]
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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. (c) 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 452-462, 2015
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