Prithi Rajan | PubMed Health

PubMed2006

Neural stem cells and their manipulation.

Extracellular signals dictate the biological processes of neural stem cells (NSCs) both in vivo and in vitro. The intracellular response elicited by these signals is dependent on the context in which the signal is received, which in turn is decided by previous and concurrent signals impinging on the cell. A synthesis of signaling pathways that control proliferation, survival, and differentiation of NSCs in vivo and in vitro will lead to a better understanding of their biology, and will also permit more precise and reproducible manipulation of these cells to particular end points. In this review we summarize the known signals that cause proliferation, survival, and differentiation in mammalian NSCs.

Cell Culture Techniques↗

PubMed2003

BMPs signal alternately through a SMAD or FRAP-STAT pathway to regulate fate choice in CNS stem cells.

The ability of stem cells to generate distinct fates is critical for the generation of cellular diversity during development. Central nervous system (CNS) stem cells respond to bone morphogenetic protein (BMP) 4 by differentiating into a wide variety of dorsal CNS and neural crest cell types. We show that distinct mechanisms are responsible for the generation of two of these cell types, smooth muscle and glia. Smooth muscle differentiation requires BMP-mediated Smad1/5/8 activation and predominates where local cell density is low. In contrast, glial differentiation predominates at high local densities in response to BMP4 and is specifically blocked by a dominant-negative mutant Stat3. Upon BMP4 treatment, the serine-threonine kinase FKBP12/rapamycin-associated protein (FRAP), mammalian target of rapamycin (mTOR), associates with Stat3 and facilitates STAT activation. Inhibition of FRAP prevents STAT activation and glial differentiation. Thus, glial differentiation by BMP4 occurs by a novel pathway mediated by FRAP and STAT proteins. These results suggest that a single ligand can regulate cell fate by activating distinct cytoplasmic signals.

Animals↗