CHL1 negatively regulates the proliferation and neuronal differentiation of neural progenitor cells through activation of the ERK1/2 MAPK pathway

Xin Huang, Ling ling Zhu, Tong Zhao, Li ying Wu, Kui wu Wu, Melitta Camartin, Zhi Cheng Xiao, Ming Fan

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Neural recognition molecules of the immunoglobulin superfamily play important roles in the development and regeneration of nervous system. Close Homologue of L1 (CHL1) is a member of the L1 family of recognition molecules which are expressed during neuronal development, suggesting a potential role in neural progenitor cells (NPCs). Here, we investigated the role of CHL1 in the proliferation and differentiation of NPCs both in vivo and in vitro, and the possible mechanism involved. The number of BrdU-positive cells in the subventricular zone (SVZ) significantly increased in CHL1-/- mice compared with CHL1+/+ mice. Moreover, there were more Tuj1-positive cells in the cortical plate region in CHL1-/- mice than in CHL1+/+ controls. To further examine the function of CHL1 in the proliferation and differentiation of NPCs, NPCs from CHL1-/- mice versus littermate wild-type mice were isolated and cultured in vitro. NPCs derived from CHL1-/- mice showed increased proliferation and self-renewal ability compared with CHL1+/+ mice. In the course of differentiation, CHL1 deficiency enhanced neuronal differentiation in the absence of growth factors. Furthermore, CHL1 deficiency on the proliferation of NPCs is accompanied by means of enhanced activation of ERK1/2 mitogen-activated protein kinase (MAPK) and the inhibitor of ERK1/2 MAPK eliminates the effect of CHL1 deficiency on the proliferation of NPCs. Our results first describe the negative modulation of the proliferation and neuronal differentiation of NPCs by CHL1/ERK1/2 MAPK signaling.

Original languageEnglish (US)
Pages (from-to)296-307
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Keywords

  • CHL1
  • Differentiation
  • ERK1/2 MAPK
  • Neural progenitor cells
  • Proliferation

Fingerprint Dive into the research topics of 'CHL1 negatively regulates the proliferation and neuronal differentiation of neural progenitor cells through activation of the ERK1/2 MAPK pathway'. Together they form a unique fingerprint.

Cite this