Inducible expression of noggin selectively expands neural progenitors in the adult SVZ

• Transgenic expression of noggin in the SVZ increases the numbers of C and A cells.
• Noggin promotes differentiation of oligodendrocyte progenitor cells.
• Long term noggin over-expression does not alter the cellular organization of the niche.
• Noggin promotes differentiation of neurospheres without affecting self-renewal.
• A novel microRNA is induced by noggin over-expression.

Multipotent, self-renewing stem cells are present throughout the developing nervous system remaining in discrete regions of the adult brain. In the subventricular zone (SVZ) signaling molecules, including the bone morphogenetic proteins and their secreted inhibitor, noggin appear to play a critical role in controlling neural stem cell (NSC) behavior. To examine the function of this signaling pathway in the intact nervous system, we developed a transgenic mouse model in which noggin expression can be induced specifically in NSC via a nestin-driven reverse tetracycline-controlled transactivator (rtTA). In adult animals, the induction of noggin expression promotes the proliferation of neural progenitors in the SVZ, and shifts the differentiation of B cells (NSC) from mature astrocytes to transit amplifying C cells and oligodendrocyte precursor cells without depleting the NSC population. Noggin expression significantly increases neuronal and oligodendrocyte differentiation both in vivo and in vitro when NSCs are grown as neurospheres. These results demonstrate that noggin/BMP interactions tightly control cell fate in the SVZ.