The proposed studies are a continuation of studies that have been ongoing for 15 years to explore the role of cytokines in regulating neural development. The proposed studies will focus on the role of the bone morphogenetic proteins (BMPs), particularly BMP4, in progenitor cell lineage commitment and brain development. Combined in vitro and in vivo approaches will assess BMP4 on progenitor cell survival, proliferation, and commitment to astrocytic and neuronal lineages. The first set of studies the differential effects of BMP on the genesis and fate of progenitor cells from the ventricular (VZ) and subventricular zones (SVZ) in vitro. These studies will include examining the role of epidermal growth factor receptor (EGF) signaling as modulating the effects of BMP, examining the effects of BMP on neuronal differentiation and survival. The second set of studies will define the actions of BMP4 in vivo using transgenic animals in which a glial fibrillary acidic acid promoter (GBMP) or a neuron specific enolase promoter (NSEBMP) drives overexpression of BMP4. These transgenic animals will allow examination of effects of BMP4 on the genesis and fate of the developing brain in vivo, including the regulation of neuronal differentiation. These studies will test the hypotheses that the BMPs promote astrocytic, but suppress oligodendroglial lineage commitment, in the developing brain, and that they regulate growth of dendrites and/or axons from specific populations of cortical, hippocampal, and cerebellar neurons.
Showing the most recent 10 out of 122 publications
