Bone morphogenetic protein 4 stimulates attachment of neurospheres and astrogenesis of neural stem cells in neurospheres via phosphatidylinositol 3 kinase-mediated upregulation of N-cadherin

M. Y. Kim, S. Kaduwal, D. H. Yang, K. Y. Choi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The neurosphere culture system is useful for expanding neural stem cells (NSCs) without affecting self-renewal potential and multipotency. However, the extrinsic signals that affect the formation or dissociation of neurospheres are poorly understood. Here, we found that bone morphogenetic protein 4 (BMP4) induced the attachment of neurospheres, astrocytic differentiation, and migration of neurosphere NSCs. These outcomes were accompanied by Akt activation and upregulation of the adhesion molecule, N-cadherin. A phosphatidylinositol 3 kinase (PI3 kinase) inhibitor (LY294002) blocked attachment of neurosphere, astrocytic differentiation, migration, and N-cadherin upregulation of neurosphre NSCs. The PI3 kinase-Akt pathway appeared to selectively mediate the effects of BMP4, as neurosphere attachment was unaffected by MEK inhibitors (PD98059 and U0126). Importantly, a neutralizing N-cadherin antibody inhibited BMP4-induced neurosphere attachment, astrocytic differentiation, and migration of neurosphere NSCs. Together, these findings show that BMP4-induced attachment of neurospheres is related to the astrocytic differentiation of these cells and that these effects are attributable, at least in part, to PI3 kinase-Akt pathway-dependent induction of N-cadherin.

Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalNeuroscience
Volume170
Issue number1
DOIs
Publication statusPublished - 2010 Sep 1

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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