title: The epigenetic factor Kmt2a/Mll1 regulates neural progenitor proliferation and neuronal and glial differentiation.
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.
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yin-Cheng
authors.initials: YC
authors.lastname: Huang
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Shih
authors.forename: Sheng-Jia
authors.initials: SJ
authors.lastname: Lin
authors.forename: Ching-Chi
authors.initials: CC
authors.lastname: Chiu
authors.forename: Tsu-Lin
authors.initials: TL
authors.lastname: Ma
authors.forename: Tu-Hsueh
authors.initials: TH
authors.lastname: Yeh
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000502:physiology; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D011495:Histone-Lysine N-Methyltransferase; C000604809:Kmt2a protein, Zebra Fish
keywords: Kmt2a; differentiation; neural progenitors; proliferation; zebrafish