Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression
Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression
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DOI：
10.1073/pnas.0605699104
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发表时间：
2007-03-20
影响因子：
11.1
通讯作者：
Soriano, Eduardo
中科院分区：
文献类型：
--
作者：
Pascual, Marta;Abasolo, Ibane;Soriano, Eduardo
我们在这项研究中报告说，在小脑中，胰腺转录因子 Ptf1a 对于浦肯野细胞 (PC) 和中间神经元的特定生成是必需的。此外，外部 GCL (EGL) 中的颗粒细胞祖细胞似乎不受 Ptf1a 缺失的影响。 Ptf1a(Cre/Cre) 小鼠的细胞谱系分析用于确定，在缺乏 Ptf1a 表达的情况下，通常注定要产生 PC 和中间神经元的心室区祖细胞会异常迁移到 EGL 并表达这些细胞的典型标记，例如 Math1、Reelin 和 Zic1/2。此外，这些细胞具有 EGL 祖细胞典型的精细结构，表明它们采用 EGL 样细胞表型。这些发现表明 Ptf1a 对于 PC 和小脑中间神经元的规范和正常产生是必需的。此外，我们的结果表明 Ptf1a 也是抑制小脑室区前体颗粒细胞规范程序所必需的。
We report in this study that, in the cerebellum, the pancreatic transcription factor Ptf1a is required for the specific generation of Purkinje cells (PCs) and interneurons. Moreover, granule cell progenitors in the external GCL (EGL) appear to be unaffected by deletion of Ptf1a. Cell lineage analysis in Ptf1a(Cre/Cre) mice was used to establish that, in the absence of Ptf1a expression, ventricular zone progenitors, normally fated to produce PCs and interneurons, aberrantly migrate to the EGL and express typical markers of these cells, such as Math1, Reelin, and Zic1/2. Furthermore, these cells have a fine structure typical of EGL progenitors, indicating that they adopt an EGL-like cell phenotype. These findings indicate that Ptf1a is necessary for the specification and normal production of PCs and cerebellar interneurons. Moreover, our results suggest that Ptf1a is also required for the suppression of the granule cell specification program in cerebellar ventricular zone precursors.