Embryonic development of olfactory bulb interneurons

University Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION (provided by applicant): During development, distinct subtypes of interneurons are produced according to regional subdivision of the basal forebrain. Olfactory bulb (OB) interneurons are produced by progenitors in the lateral ganglionic eminence (LGE), and cortical and striatal interneurons are produced by progenitors in the medial ganglionic eminence (MGE). The current proposal uses in vitro migration and differentiation assays to examine whether position in the LGE or the expression of LGE-enriched transcription factors regulate the genesis of OB interneurons. By grafting MGE cells into the LGE and LGE cells into the MGE, we will ask if extrinsic factors regulate the acquisition of cell fate. By misexpressing LGE-enriched factors (Er81, Gsh2, and Pax6) in MGE cells and MGE-enriched factors (Nkx2.1 and Lhx6) in LGE cells, we will determine whether regionally expressed transcriptional regulators modulate cell identity. Finally, we will assess the autonomy of Pax6 and Gsh2 in producing OB interneurons by analyzing the migration and differentiation of mutant cells. The long-term objective of the proposed study is to determine how autonomous and non-autonomous factors influence the production of unique subtypes of neurons in the mammalian forebrain.