Active intermixing of indirect and direct neurons builds the striatal mosaic.

Active intermixing of indirect and direct neurons builds the striatal mosaic.
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DOI:
10.1038/s41467-018-07171-4
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发表时间:
2018-11-09
影响因子:
16.6
通讯作者:
Garel S
Garel S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tinterri A;Menardy F;Diana MA;Lokmane L;Keita M;Coulpier F;Lemoine S;Mailhes C;Mathieu B;Merchan-Sala P;Campbell K;Gyory I;Grosschedl R;Popa D;Garel S

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纹状体通过混合在所有隔室中的直接和间接通路投射神经元(dSPN和iSPN)的活动来控制行为。虽然这种细胞镶嵌确保了两种途径的平衡活性,但其发育起源和模式在很大程度上仍然未知。在这里,我们表明,这两个SPN人口指定胚胎和混合逐步通过多向iSPN迁移。使用条件突变小鼠,我们发现dSPN特异性转录因子Ebf 1的失活损害了选择性dSPN特性,包括轴突寻路,而iSPN的分子和功能特征被保留。Ebf 1突变破坏了iSPN/dSPN的混合,导致分布不均匀。这种结构缺陷对基质隔室具有选择性,突出表明混合是隔室形成的平行过程。我们的研究表明,虽然iSPN/dSPN规范在很大程度上是独立的,但它们的混合来自iSPN的主动迁移,从而为纹状体结构的构建提供了一个新的框架。纹状体投射神经元作为两种不同的类别存在,并且在脑中解剖学上是混合的。在这里,Tinterri和他的同事们展示了这种细胞镶嵌的发育机制,这种机制依赖于细胞类型特异性和混合细胞迁移的内在转录因子。
The striatum controls behaviors via the activity of direct and indirect pathway projection neurons (dSPN and iSPN) that are intermingled in all compartments. While such cellular mosaic ensures the balanced activity of the two pathways, its developmental origin and pattern remains largely unknown. Here, we show that both SPN populations are specified embryonically and intermix progressively through multidirectional iSPN migration. Using conditional mutant mice, we found that inactivation of the dSPN-specific transcription factor Ebf1 impairs selective dSPN properties, including axon pathfinding, while molecular and functional features of iSPN were preserved. Ebf1 mutation disrupted iSPN/dSPN intermixing, resulting in an uneven distribution. Such architectural defect was selective of the matrix compartment, highlighting that intermixing is a parallel process to compartment formation. Our study reveals while iSPN/dSPN specification is largely independent, their intermingling emerges from an active migration of iSPN, thereby providing a novel framework for the building of striatal architecture. Striatal projection neurons exist as two distinct classes and are anatomically mixed in the brain. Here, Tinterri and colleagues show the developmental mechanism of this cellular mosaicism that relies on an intrinsic transcription factor for cell type specification and intermixed cellular migration.
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