title: Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation.
abstract: Maternal embryonic leucine zipper kinase (MELK) was previously identified in a screen for genes enriched in neural progenitors. Here, we demonstrate expression of MELK by progenitors in developing and adult brain and that MELK serves as a marker for self-renewing multipotent neural progenitors (MNPs) in cultures derived from the developing forebrain and in transgenic mice. Overexpression of MELK enhances (whereas knockdown diminishes) the ability to generate neurospheres from MNPs, indicating a function in self-renewal. MELK down-regulation disrupts the production of neurogenic MNP from glial fibrillary acidic protein (GFAP)-positive progenitors in vitro. MELK expression in MNP is cell cycle regulated and inhibition of MELK expression down-regulates the expression of B-myb, which is shown to also mediate MNP proliferation. These findings indicate that MELK is necessary for proliferation of embryonic and postnatal MNP and suggest that it regulates the transition from GFAP-expressing progenitors to rapid amplifying progenitors in the postnatal brain.
authors.affiliation: Department of Pharmacology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakano
authors.forename: Andres A
authors.initials: AA
authors.lastname: Paucar
authors.forename: Ruchi
authors.initials: R
authors.lastname: Bajpai
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Dougherty
authors.forename: Amani
authors.initials: A
authors.lastname: Zewail
authors.forename: Theresa K
authors.initials: TK
authors.lastname: Kelly
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kim
authors.forename: Jing
authors.initials: J
authors.lastname: Ou
authors.forename: Matthias
authors.initials: M
authors.lastname: Groszer
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Imura
authors.forename: William A
authors.initials: WA
authors.lastname: Freije
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sofroniew
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Terskikh
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Harley I
authors.initials: HI
authors.lastname: Kornblum
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C499306:Mybl2 protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; C108524:Melk protein, mouse; D017346:Protein Serine-Threonine Kinases