Molecular markers of neuronal progenitors in the embryonic cerebellar anlage
Molecular markers of neuronal progenitors in the embryonic cerebellar anlage
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DOI：
10.1523/jneurosci.3493-06.2006
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发表时间：
2006-11-22
影响因子：
5.3
通讯作者：
Hatten, Mary E.
中科院分区：
文献类型：
--
作者：
Morales, Daniver;Hatten, Mary E.
小脑与大脑一样，包括核结构和覆盖的皮质结构。过去十年的实验已经将知识扩展到小脑的传统功能之外，包括在运动学习、记忆和感觉辨别中的关键作用。小脑发育的初始步骤取决于涉及中脑/后脑边界产生的 FGF 和 Wnt 蛋白的诱导信号传导。为了解决小脑区域内个体小脑细胞命运如何被指定的问题，我们检查了转录因子的表达，包括含有 LIM 同源域的蛋白质的哺乳动物同源物、碱性螺旋-环-螺旋蛋白和三种含有氨基酸环的蛋白质。这些研究的结果表明，转录因子的组合编码定义了小脑核的前体以及小脑皮质的浦肯野细胞和颗粒神经元。 GENSAT 项目对数百个 Egfp-BAC（细菌人工染色体）转基因小鼠的基因表达模式进行了检查，发现许多基因在小脑祖细胞群中表达受限，包括小脑核前体和浦肯野细胞前体的特异性基因。此外，我们还确定了将颗粒细胞和浦肯野细胞与其小脑前核联系起来的基因表达模式。这些结果确定了分子途径，为小脑的核结构和皮质结构以及小脑回路的组成部分的发育提供了新的见解。
The cerebellum, like the cerebrum, includes a nuclear structure and an overlying cortical structure. Experiments in the past decade have expanded knowledge beyond the traditional function of the cerebellum to include critical roles in motor learning and memory and sensory discrimination. The initial steps in cerebellar development depend on inductive signaling involving FGF and Wnt proteins produced at the mesencephalic/metencephalic boundary. To address the issue of how individual cerebellar cell fates within the cerebellar territory are specified, we examined the expression of transcription factors, including mammalian homologues of LIM homeodomain-containing proteins, basic helix-loop-helix proteins, and three amino acid loop-containing proteins. The results of these studies show that combinatorial codes of transcription factors define precursors of the cerebellar nuclei, and both Purkinje cells and granule neurons of the cerebellar cortex. Examination of gene expression patterns in several hundred lines of Egfp-BAC (bacterial artificial chromosome) transgenic mice in the GENSAT Project revealed numerous genes with restricted expression in cerebellar progenitor populations, including genes specific for cerebellar nuclear precursors and Purkinje cell precursors. In addition, we identified patterns of gene expression that link granule and Purkinje cells to their precerebellar nuclei. These results identify molecular pathways that offer new insights on the development of the nuclear and cortical structures of the cerebellum, as well as components of the cerebellar circuitry.