BASIC MOLECULAR FINGERPRINTING OF IMMATURE CEREBELLAR CORTICAL INHIBITORY INTERNEURONS AND THEIR PRECURSORS
BASIC MOLECULAR FINGERPRINTING OF IMMATURE CEREBELLAR CORTICAL INHIBITORY INTERNEURONS AND THEIR PRECURSORS
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DOI：
10.1016/j.neuroscience.2008.12.016
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发表时间：
2009-03-03
期刊：
影响因子：
3.3
通讯作者：
Schilling, K.
中科院分区：
文献类型：
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作者：
Glassmann, A.;Topka, S.;Schilling, K.
虽然小脑颗粒神经元和浦肯野神经元的发育已被广泛研究，但对小脑皮层抑制性gaba能中间神经元的产生和分化的发育机制知之甚少。为了解决这个问题，我们比较了完整的、早期出生的小鼠小脑与未成熟的抑制性中间神经元及其前体被剥离的小脑中的基因表达，基于它们在Pax2位点的绿色荧光蛋白（GFP）的表达。我们在未成熟的小脑皮质抑制性中间神经元和/或其前体中选择性地富集了大约300个候选基因，其中许多基因也在它们的成年后代和/或胚胎小脑室上皮中表达，从而产生这些细胞。其中，Tcfap2 α、Tcfap2 β、Lbxcor1和Lbx1基因均不具有细胞特异性。相反，基因表达和剪接在发育过程中是动态变化的，反映的是分化阶段而不是谱系。一致地，对成年小脑gaba能细胞的转录调节因子和特异性基因的聚类分析并没有提示等级谱系关系或小脑皮质抑制性中间神经元亚型的早期承诺。综上所述，这些数据支持了小脑抑制性中间神经元的多样化是高度调控的，并受局部信号传导到迁移后前体的影响。(c) 2009 ibro。Elsevier Ltd.出版。版权所有。
While the development of cerebellar granule and Purkinje neurons has been extensively studied, little is known about the developmental mechanisms that lead to the generation and diversification of inhibitory GABAergic interneurons of the cerebellar cortex. To address this issue, we compared gene expression in complete, early postnatal murine cerebella to that in cerebella from which immature inhibitory interneurons and their precursors had been stripped based on their expression of green fluorescent protein (GFP) from the Pax2 locus. We identified some 300 candidate genes selectively enriched within immature cerebellar cortical inhibitory interneurons and/or their precursors, many of which were also expressed in their adult descendants and/or the embryonic cerebellar ventricular epithelium that gives rise to these cells. None of the genes identified, among them Tcfap2 alpha, Tcfap2 beta, Lbxcor1 and Lbx1, was cell-type specific. Rather, gene expression, and also splicing, changed dynamically during development and rather reflects stage of differentiation than lineage. Consistently, cluster analysis of transcriptional regulators and genes specific for adult cerebellar GABAergic cells does not suggest a hierarchical lineage relationship or an early commitment of subtypes of cerebellar cortical inhibitory interneurons. Together, these data support the notion that diversification of cerebellar inhibitory interneurons is highly regulative and subject to local signaling to postmigratory precursors. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.