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.
|Number of pages||8|
|Publication status||Published - 2010 Sep|
Bibliographical noteFunding Information:
This work was supported by National Research Foundation (NRF) grant funded by the Ministry of Education, Science and Technology of Korea government (MEST) ( Translational Research Center for Protein Function Control ; 2010-0001919 , and Stem Cell Project ; 2010-0020235 ). Mi-Yeon Kim, Saluja Kadwal, and Dong-Hwa Yang were supported by a BK21 studentship from the NRF .
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