BMP Antagonism and the Regulation of Neural Stem Cells
In the adult mammalian brain, the subventricular zone (SVZ) of the lateral ventricular wall produces large numbers of neurons throughout life. The structural and molecular characteristics of the cells present in the SVZ have been described, as has the lineage from stem cell to committed neuroblast. However, the molecular mechanisms that govern the stem cell properties of this population are poorly understood. The Harland lab has a long-standing interest in the roles BMPs and BMP antagonists play during vertebrate development. The secreted BMP antagonist Noggin, BMPs, and their cognate receptors are expressed in the SVZ. In addition, previous work from other labs has suggested that BMP signaling regulates the behavior of neural progenitors. Nevertheless, no mutants in the BMP signaling pathway have been tested for defects in neural stem cell regulation. As conventional null noggin mutant mice die at birth, we are using our conditional noggin allele to test the hypothesis that by antagonizing BMP, Noggin promotes SVZ stem cell differentiation.
