The roles of Id protein in CNS glial fate decisions

Columbia University Health Sciences, New York NY

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Abstract

DESCRIPTION (provided by applicant): How CNS stem cells and progenitors regulate fate decisions to neurons and glia is a critical problem in developmental neurobiology and is a requisite for harvesting their potential for therapeutic purposes. This proposal addresses whether the Inhibitor of DMA binding protein 3, or Id3, is a major regulator of glial fate decisions. Id proteins negatively regulate basic helix-loop-helix proteins, such as the pro-oligodendrocytic Olig2. We have been studying the perinatal subventricular zone (SVZ) which generates neurons, oligodendrocytes and astrocytes contemporaneously. I have found in preliminary studies that Id3 is expressed throughout the SVZ. SVZ cells that overexpress Id3 in vivo are strongly biased in favor of an astrocytic and against an oligodendrocytic fate. The proposed studies will determine whether the increase in relative astrocyte numbers is due to increased proliferation, survival, or generation of astrocytes. The proposal will ask whether Id3 decreases the likelihood of an oligodendrocytic fate decision, by over expressing Id3 in progenitor cells in vitro. Finally, the proposal explores whether Id3 and Olig2 collaborate in glial specification, leading to astrocyte or oligodendrocyte fates, respectively.