Septal contributions to olfactory bulb interneuron diversity in the embryonic mouse telencephalon: role of the homeobox gene Gsx2.

Septal contributions to olfactory bulb interneuron diversity in the embryonic mouse telencephalon: role of the homeobox gene Gsx2.
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DOI:
10.1186/s13064-017-0090-5
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发表时间:
2017-08-16
期刊:
影响因子:
3.6
通讯作者:
Campbell K
Campbell K
中科院分区:
生物学3区
文献类型:
--
作者:
Qin S;Ware SM;Waclaw RR;Campbell K

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嗅球(OB)中间神经元代表多种神经元亚型,其被认为起源于包括胚胎背外侧神经节隆起(dLGE)和隔在内的许多端脑区域。这些细胞向OB迁移,然后径向迁移到不同的OB层,包括颗粒细胞层(GCL)和外肾小球层(GL)。虽然以前的研究试图调查区域的贡献OB interneuron多样性,很少有遗传工具已被用来解决这个问题,在胚胎时间点时,最早的人口被指定。在这项研究中,我们利用Zic 3-lacZ和Gsx 2 e-CIE转基因小鼠的遗传命运映射工具,研究OB中间神经元的贡献来自隔和LGE,分别。此外,为了解决OB中间神经元多样性的同源异型盒基因Gsx 2的区域(即间隔)要求,我们通过使用Olig 2 Cre/+小鼠重组Gsx 2 floxed等位基因,有条件地使间隔中的Gsx 2失活,使其在dLGE中基本上保持完整。我们的命运定位研究表明,dLGE和隔引起OB中间神经元亚型不同。值得注意的是,发现胚胎隔膜主要产生钙视网膜蛋白+(CR+)GL亚型,而dLGE更多样化,产生所有主要GL亚群以及许多GCL中间神经元。此外,Gsx 2条件突变体(cKO),隔膜,但不dLGE重组,表现出受损的一代CR+ interneurons内的OB GL。这些Gsx 2 cKO表现出室间隔下区(SVZ)内增殖减少,这与观察到的CR+中间神经元数量减少密切相关。我们的研究结果表明,隔和LGE有助于不同的OB中间神经元的多样性。虽然dLGE提供了广泛的OB中间神经元亚型,但隔膜对CR+亚型的贡献更受限制。Gsx 2在隔祖细胞中是需要的,用于SVZ祖细胞向CR+亚型的正确扩增。最后,在出生后的研究中,隔被认为是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。本文的在线版本(doi:10.1186/s13064-017-0090-5)包含补充材料,可供授权用户使用。
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. 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. 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. 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. The online version of this article (doi:10.1186/s13064-017-0090-5) contains supplementary material, which is available to authorized users.
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