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兴奋性颗粒神经元前体细胞协调小脑抑制性中间神经元亚型的层定位和分化。

Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtypes.

机构信息

IGF, University Montpellier, CNRS, INSERM, Montpellier, France.

Institut Curie, Université PSL, CNRS UMR3347, INSERM U1021, Signaling Radiobiology and Cancer, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3347, INSERM U1021, Signaling Radiobiology and Cancer, 91400 Orsay, France.

出版信息

Cell Rep. 2021 Mar 30;34(13):108904. doi: 10.1016/j.celrep.2021.108904.

Abstract

GABAergic interneurons migrate long distances through stereotyped migration programs toward specific laminar positions. During their migration, GABAergic interneurons are morphologically alike but then differentiate into a rich array of interneuron subtypes critical for brain function. How interneuron subtypes acquire their final phenotypic traits remains largely unknown. Here, we show that cerebellar molecular layer GABAergic interneurons, derived from the same progenitor pool, use separate migration paths to reach their laminar position and differentiate into distinct basket cell (BC) and stellate cell (SC) GABAergic interneuron subtypes. Using two-photon live imaging, we find that SC final laminar position requires an extra step of tangential migration supported by a subpopulation of glutamatergic granule cells (GCs). Conditional depletion of GCs affects SC differentiation but does not affect BCs. Our results reveal how timely feedforward control of inhibitory interneuron migration path regulates their terminal differentiation and, thus, establishment of the local inhibitory circuit assembly.

摘要

GABA 能中间神经元通过向特定层位迁移的刻板迁移程序进行长距离迁移。在迁移过程中,GABA 能中间神经元在形态上相似,但随后分化为丰富的中间神经元亚型,这些亚型对大脑功能至关重要。中间神经元亚型如何获得最终的表型特征在很大程度上仍是未知的。在这里,我们表明,来自同一祖细胞池的小脑分子层 GABA 能中间神经元使用不同的迁移路径到达其层位,并分化为不同的篮状细胞 (BC) 和星状细胞 (SC) GABA 能中间神经元亚型。使用双光子活体成像,我们发现 SC 的最终层位需要额外的切线迁移步骤,由一群谷氨酸能颗粒细胞 (GC) 支持。GC 的条件性耗竭会影响 SC 的分化,但不影响 BC。我们的结果揭示了抑制性中间神经元迁移路径的适时前馈控制如何调节其终末分化,从而建立局部抑制性回路的组装。

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