Embryonic development of olfactory bulb interneurons

描述（由申请人提供）：在发育过程中，根据基底前脑的区域细分，产生不同亚型的中间神经元。嗅球（OB）中间神经元由外侧神经节隆起（LGE）的祖细胞产生，皮层和纹状体中间神经元由内侧神经节隆起（MGE）的祖细胞产生。目前的建议使用体外迁移和分化实验来检查LGE中的位置或富含LGE的转录因子的表达是否调节OB中间神经元的发生。通过将MGE细胞移植到LGE中，将LGE细胞移植到MGE中，我们将探讨外部因素是否调节了细胞的获得命运。通过在MGE细胞中错表达LGE富集因子（Er81、Gsh2和Pax6）以及在LGE细胞中错表达MGE富集因子（Nkx2.1和Lhx6），我们将确定区域表达的转录调节因子是否会调节细胞身份。最后，我们将通过分析突变细胞的迁移和分化来评估Pax6和Gsh2在产生OB中间神经元中的自主性。该研究的长期目标是确定自主和非自主因素如何影响哺乳动物前脑中独特神经元亚型的产生。

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.