Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation

Ichiro Nakano, Andres A. Paucar, Ruchi Bajpai, Joseph D. Dougherty, Amani Zewail, Theresa K. Kelly, Kevin J. Kim, Jing Ou, Matthias Groszer, Tetsuya Imura, William A. Freije, Stanley F. Nelson, Michael V. Sofroniew, Hong Wu, Xin Liu, Alexey V. Terskikh, Daniel H. Geschwind, Harley I. Kornblum

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

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.

Original languageEnglish
Pages (from-to)413-427
Number of pages15
JournalJournal of Cell Biology
Volume170
Issue number3
DOIs
StatePublished - 1 Sep 2005
Externally publishedYes

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