Correct coordination of neuronal differentiation events in ventral forebrain requires the bHLH factor MASH1
Correct coordination of neuronal differentiation events in ventral forebrain requires the bHLH factor MASH1
复制标题
腹侧前脑中神经元分化事件的正确协调需要 bHLH 因子 MASH1
DOI：
10.1006/mcne.1999.0791
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发表时间：
1999-10-01
影响因子：
3.5
通讯作者：
Johnson, JE
中科院分区：
文献类型：
--
作者：
Horton, S;Meredith, A;Johnson, JE
MASH 1是一种在发育中的神经系统中特异性表达的bHLH转录因子，在外周和中枢神经系统中多种神经元谱系的形成中具有重要作用。在这里，我们证明了MAsH 1腹侧前脑结构的正常发育的要求。MASH 1在腹侧端脑和腹侧间脑内的特定区域中以高水平表达。在没有MAsH 1的情况下，这些前脑区域内的组织形态、增殖和基因表达被破坏。神经上皮中BrdU掺入减少和脑室扩大表明细胞增殖减少。解剖学上不同的外侧和内侧神经节隆起的丢失，以及穿过该区域的轴突的破坏，表明细胞类型特异性异常。Tuj-1（神经上皮细胞中神经元分化的标志物）和nix（区域细胞身份的标志物）在MAsH 1突变体脑的脑室区中的异常表达表明分化事件的协调被破坏。此外，MASH 1参与影响这些前脑区域发育的侧抑制过程。两者合计，MASH 1在协调事件所需的正确的细胞类型规范和分化的时间在腹侧前脑区域的神经发育过程中的重要作用被证明。
MASH1 is a bHLH transcription factor specifically expressed in the developing nervous system that has an essential role in the formation of multiple neuronal lineages in the peripheral and central nervous systems. Here we demonstrate the requirement for MAsH1 for normal development of ventral forebrain structures. MASH1 is expressed at high levels in the ventral telencephalon and specific regions within the ventral diencephalon. In the absence of MAsH1, tissue morphology, proliferation, and gene expression within these forebrain regions is disrupted. The decreased incorporation of BrdU in the neuroepithelium and the enlargement of the ventricles demonstrate a reduction in cell proliferation. A loss of anatomically distinct lateral and medial ganglionic eminences, end a disruption of axons traversing this region, indicate abnormalities in cell-type specification. The aberrant expression of Tuj-1, a marker of neuronal differentiation in the neuroepithelium, and nix, a marker of regional cell identity, in the ventricular zone in the MAsH1 mutant brains suggest coordination of differentiation events is disrupted. In addition, the involvement of MASH1 in lateral inhibition processes that affect the development of these forebrain regions is implicated. Taken together, an essential role for MAsH1 in the coordination of events required for correct cell-type specification and timing of differentiation during neural development in ventral forebrain regions is demonstrated.