Inductive interactions direct early regionalization of the mouse forebrain.
Inductive interactions direct early regionalization of the mouse forebrain.
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DOI：
10.1242/dev.124.14.2709
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发表时间：
1997-07
期刊：
影响因子：
4.6
通讯作者：
K. Shimamura;J. Rubenstein
中科院分区：
文献类型：
--
作者：
K. Shimamura;J. Rubenstein
调控前脑区域规范的细胞和分子机制在很大程度上是未知的。我们研究了神经板外植体中转录因子的表达，以确定调节前脑神经板内侧外侧和局部模式的组织及其产生的分子。内侧神经板的分子特性可能通过Sonic Hedgehog的作用受到脊索前板的调控。相反，侧神经板中的基因表达受非神经外胚层和骨形态发生蛋白的调控。这表明前脑采用与中枢神经系统其他部分相同的内侧-外侧（腹侧-背侧）模式机制。我们还发现，前神经脊调节前神经板的模式，可能是通过一种不同于调节一般内侧-外侧模式的机制。前神经嵴对BF1的表达至关重要，BF1是一种编码端脑和视神经囊泡区域化和生长所需转录因子的基因。此外，前神经脊表达Fgf8，重组Fgf8蛋白能够诱导BF1，提示Fgf8调控前外侧神经板衍生物的发育。此外，我们提供的证据表明，神经板被细分为不同的前后区域，这些区域对来自脊索前板、Sonic Hedgehog、前神经脊和FGF8的感应信号有不同的响应。总之，这些结果表明，前脑原基的区域化是由几种不同的模式机制建立的：(1)前后模式在神经板内产生具有不同能力的横向区域；(2)沿内侧-外侧轴的模式产生纵向对齐的区域；(3)局部诱导相互作用，如来自前神经脊的信号，进一步定义了区域组织。
The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic neural plate. Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization.