Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo
Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo
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DOI：
10.1016/j.neuron.2004.12.036
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发表时间：
2005-01-20
期刊：
影响因子：
16.2
通讯作者：
Macklis, JD
中科院分区：
文献类型：
--
作者：
Arlotta, P;Molyneaux, BJ;Macklis, JD
在脊椎动物神经系统内，许多不同谱系的神经元和神经胶质细胞的存在使单个神经元群体的分子表征变得复杂。为了阐明皮质脊髓运动神经元（CSMN）规范和发育的分子机制，我们在体内纯化了处于不同发育阶段的CSMN，并将其基因表达与另外两个纯皮质投射神经元群体：胼胝体投射神经元和皮质顶盖投射神经元进行了比较。我们发现了对 CSMN 发育具有潜在指导作用的基因，以及被排除在 CSMN 之外并仅限于其他神经元群（即使在同一皮质层内）的基因。 Ctip2（也称为 Bcl1 1b）是新鉴定的基因之一，在无效突变小鼠中进行的功能丧失实验表明，它在体内 CSMN 轴突投射到脊髓的发育中发挥着关键作用，证实了我们确定了 CSMN 群体的中心遗传决定因素。
Within the vertebrate nervous system, the presence of many different lineages of neurons and glia complicates the molecular characterization of single neuronal populations. In order to elucidate molecular mechanisms underlying the specification and development of corticospinal motor neurons (CSMN), we purified CSMN at distinct stages of development in vivo and compared their gene expression to two other pure populations of cortical projection neurons: callosal projection neurons and corticotectal projection neurons. We found genes that are potentially instructive for CSMN development, as well as genes that are excluded from CSMN and are restricted to other populations of neurons, even within the same cortical layer. Loss-of-function experiments in null mutant mice for Ctip2 (also known as Bcl1 1b), one of the newly characterized genes, demonstrate that it plays a critical role in the development of CSMN axonal projections to the spinal cord in vivo, confirming that we identified central genetic determinants of the CSMN population.