PDGF Responsive Progenitors of the Subventricular Zone

Abstract The subventricular zone (SVZ) contains neural stem cells and progenitors of various potentialities. Although initially parsed into A, B, and C cells, it is clear that this germinal zone is comprised of a significantly more diverse population of cells. We have established a flow cytometry panel that has revealed the existence of neural stem cells as well as 4 types of multipotential transit amplifying progenitors (TAPs) and 3 types of glial restricted TAPs. One of these TAPs, the platelet-derived growth factor (PDGF) and fibroblast growth factor-responsive multipotential progenitor (PFMP) expresses the PDGF? receptor and proliferates in response to PDGF. The other PDGFR?+ cell is a bipotential glial restricted TAP (GRP3). The central premise of this application is that the PDGF-responsive progenitors (PRPs) represent an important subset about which little is known. We provide preliminary data that suggest that these PRPs are descended from the lateral ganglionic eminence and that their proliferation can be positively and negatively affected by environmental signals. Therefore, the goal of this exploratory R21 is to: 1) Establish when the PFMPs and GRP3s emerge during mouse development; 2) Define the transcripts expressed by individual PRPs using the dropseq method and then use the Monocle algorithm to identify unique subpopulations. We will then proceed to compare and contrast the transcriptional profiles of the PRP subgroups to each other and to the stem cells (using both our data, and publicly available data) to define changes in gene transcription that correspond with their developmental restriction and specification; and 3) Establish which more restricted progenitors are descended from the PFMPs and define the types of neurons and glia that they produce in vivo. These formative studies will lay the foundation for a decade of future work to understand how these progenitors participate in neural development across species, how they are affected by environmental stimuli that disturb normal brain development leading to brain disorders and how these progenitors might be recruited to participate in regeneration and repair of the nervous system after injury.