BACKGROUND Olfactory bulb (OB) interneurons are known to represent diverse neuronal subtypes, which are thought to originate from a number of telencephalic regions including the embryonic dorsal lateral ganglionic eminence (dLGE) and septum. These cells migrate rostrally toward the OB, where they then radially migrate to populate different OB layers including the granule cell layer (GCL) and the outer glomerular layer (GL). Although previous studies have attempted to investigate regional contributions to OB interneuron diversity, few genetic tools have been used to address this question at embryonic time points when the earliest populations are specified. METHODS In this study, we utilized Zic3-lacZ and Gsx2e-CIE transgenic mice as genetic fate-mapping tools to study OB interneuron contributions derived from septum and LGE, respectively. Moreover, to address the regional (i.e. septal) requirements of the homeobox gene Gsx2 for OB interneuron diversity, we conditionally inactivated Gsx2 in the septum, leaving it largely intact in the dLGE, by recombining the Gsx2 floxed allele using Olig2 Cre/+ mice. RESULTS Our fate mapping studies demonstrated that the dLGE and septum gave rise to OB interneuron subtypes differently. Notably, the embryonic septum was found to give rise largely to the calretinin+ (CR+) GL subtype, while the dLGE was more diverse, generating all major GL subpopulations as well as many GCL interneurons. Moreover, Gsx2 conditional mutants (cKOs), with septum but not dLGE recombination, showed impaired generation of CR+ interneurons within the OB GL. These Gsx2 cKOs exhibited reduced proliferation within the septal subventricular zone (SVZ), which correlated well with the reduced number of CR+ interneurons observed. CONCLUSIONS Our findings indicate that the septum and LGE contribute differently to OB interneuron diversity. While the dLGE provides a wide range of OB interneuron subtypes, the septum is more restricted in its contribution to the CR+ subtype. Gsx2 is required in septal progenitors for the correct expansion of SVZ progenitors specified toward the CR+ subtype. Finally, the septum has been suggested to be the exclusive source of CR+ interneurons in postnatal studies. Our results here demonstrate that dLGE progenitors in the embryo also contribute to this OB neuronal subtype.

中文翻译：

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隔膜对胚胎小鼠端脑嗅球中间神经元多样性的贡献：同源框基因 Gsx2 的作用。

背景已知嗅球（OB）中间神经元代表不同的神经元亚型，这些亚型被认为起源于许多端脑区域，包括胚胎背外侧神经节隆起（dLGE）和隔膜。这些细胞向 OB 方向迁移，然后径向迁移到不同的 OB 层，包括颗粒细胞层 (GCL) 和肾小球外层 (GL)。尽管之前的研究试图调查 OB 中间神经元多样性的区域贡献，但很少有遗传工具被用来在胚胎时间点（当最早群体被指定时）解决这个问题。方法在本研究中，我们利用 Zic3-lacZ 和 Gsx2e-CIE 转基因小鼠作为遗传命运图谱工具，分别研究来自隔膜和 LGE 的 OB 中间神经元贡献。此外，为了解决同源框基因 Gsx2 对 OB 中间神经元多样性的区域（即隔膜）要求，我们通过使用 Olig2 Cre/+ 小鼠重组 Gsx2 floxed 等位基因，有条件地灭活隔膜中的 Gsx2，使其在 dLGE 中基本保持完整。结果我们的命运图谱研究表明，dLGE 和隔膜以不同的方式产生 OB 中间神经元亚型。值得注意的是，胚胎隔膜被发现主要产生钙结合蛋白+ (CR+) GL 亚型，而 dLGE 更加多样化，产生所有主要 GL 亚群以及许多 GCL 中间神经元。此外，具有隔膜但不具有 dLGE 重组的 Gsx2 条件突变体 (cKO) 显示 OB GL 内 CR+ 中间神经元的生成受损。这些 Gsx2 cKO 在间隔室下区 (SVZ) 内表现出增殖减少，这与观察到的 CR+ 中间神经元数量减少密切相关。结论 我们的研究结果表明，隔膜和 LGE 对 OB 中间神经元多样性的贡献不同。虽然 dLGE 提供了广泛的 OB 中间神经元亚型，但隔膜对 CR+ 亚型的贡献受到更多限制。为了正确扩展指定为 CR+ 亚型的 SVZ 祖细胞，间隔祖细胞中需要 Gsx2。最后，在产后研究中，隔膜被认为是 CR+ 中间神经元的唯一来源。我们的结果表明胚胎中的 dLGE 祖细胞也有助于这种 OB 神经元亚型。