Touzot Audrey, Ruiz-Reig Nuria, Vitalis Tania, Studer Michèle
Univ. Nice Sophia Antipolis, INSERM U1091, CNRS UMR7277, iBV, Nice 06100, France iBV, Institut de Biologie Valrose, Univ. Sophia Antipolis, Bâtiment Sciences Naturelles; UFR Sciences; Parc Valrose, 28, avenue Valrose, Nice Cedex 2 06108, France.
Univ. Nice Sophia Antipolis, INSERM U1091, CNRS UMR7277, iBV, Nice 06100, France iBV, Institut de Biologie Valrose, Univ. Sophia Antipolis, Bâtiment Sciences Naturelles; UFR Sciences; Parc Valrose, 28, avenue Valrose, Nice Cedex 2 06108, France Instituto de Neurociencias de Alicante (Consejo Superior de Investigaciones Cientificas-Universidad Miguel Hernandez, CSIC-UMH), Aliante 03550, Spain.
Development. 2016 May 15;143(10):1753-65. doi: 10.1242/dev.131102. Epub 2016 Mar 31.
GABAergic interneurons are highly heterogeneous and originate in the subpallium mainly from the medial (MGE) and caudal (CGE) ganglionic eminences according to a precise temporal sequence. MGE-derived cells disperse dorsally and migrate towards all regions of the cortex, but little is known about how CGE-derived cells reach their targets during development. Here, we unravel the existence of two novel CGE caudo-rostral migratory streams, one located laterally (LMS) and the other one more medially (MMS), that, together with the well-known caudal migratory stream (CMS), contribute to populate the neocortex, hippocampus and amygdala. These paths appear in a precise temporal sequence and express a distinct combination of transcription factors, such as SP8, PROX1, COUP-TFI and COUP-TFII. By inactivating COUP-TFI in developing interneurons, the lateral and medial streams are perturbed and expression of SP8 and COUP-TFII affected. As a consequence, adult mutant neocortices have laminar-specific alterations of distinct cortical interneuron subtypes. Overall, we propose that the existence of spatially and temporally regulated migratory paths in the subpallium contributes to the laminar distribution and specification of distinct interneuron subpopulations in the adult brain.
γ-氨基丁酸能中间神经元高度异质性,根据精确的时间顺序主要起源于皮质下的内侧(MGE)和尾侧(CGE)神经节隆起。源自MGE的细胞向背侧分散并迁移至皮质的所有区域,但关于源自CGE的细胞在发育过程中如何到达其靶标知之甚少。在此,我们揭示了两条新的CGE尾-头迁移流的存在,一条位于外侧(LMS),另一条更靠近内侧(MMS),它们与著名的尾侧迁移流(CMS)一起,有助于新皮质、海马体和杏仁核的细胞填充。这些路径按精确的时间顺序出现,并表达转录因子的独特组合,如SP8、PROX1、COUP-TFI和COUP-TFII。通过在发育中的中间神经元中使COUP-TFI失活,外侧和内侧迁移流受到干扰,SP8和COUP-TFII的表达也受到影响。结果,成年突变体新皮质具有不同皮质中间神经元亚型的层特异性改变。总体而言,我们认为皮质下空间和时间调控的迁移路径的存在有助于成年大脑中不同中间神经元亚群的层状分布和特异性。