The role of prdm1 in neural cell fate specification

为了产生功能性神经系统，神经祖细胞需要采用一种特定的命运， 另我实验室的长期目标是确定调节细胞增殖的分子机制， 神经嵴和Rohon-Beard感觉神经元的命运决定。神经嵴细胞和Rohon- 胡须感觉神经元起源于神经板的外侧部分，而神经嵴细胞迁移 广泛形成所有的周围神经系统（PNS;除其他衍生物），Rohon-Beard 感觉神经元保留在中枢神经系统（CNS）内。本申请的具体目的是 确定神经嵴和RB感觉神经元的祖细胞群的位置， prdm 1是否主动调节神经嵴和RB感觉的细胞增殖和/或分化 神经元，并鉴定prdml调节边缘细胞命运的分子途径的组分。 我们的假设是，prdml是至关重要的形成神经嵴和RB感觉神经元在外侧 神经板提出了一系列实验来检验这一假设。我们打算检验这个假设 神经板边界祖细胞在空间上是分离的，并且在其先天细胞能力方面受到限制， 以及它们对环境的反应能力。此外，我们还将检验以下假设：prdml的作用是 通过促进神经板边缘前体细胞的分化来指定细胞命运，而不影响 细胞增殖或细胞死亡。最后，我们将讨论prdml作为转录因子的假设， 阻遏物，以阻遏维持前体命运所需的靶基因，从而促进 分化为了实现这些目标，我们将利用斑马鱼系统，斑马鱼，因为它 已建立完善的实验和遗传方法，使这一过程的可行性进行了详细的分析。作为 这些研究的一个结果是，预计将确定prdml转录因子起关键作用， 在神经管和嵴细胞的规格。这将是重要的，在确定遗传途径 这对神经管和嵴的发育很重要，而这反过来又是 在人类先天性缺陷，如脊柱裂和唇腭裂的预防措施。

In order to generate a functional nervous system, neural progenitors need to adopt one specific fate verses another. It is the long-term goal of my laboratory to determine the molecular mechanisms that regulate cell fate determination of neural crest and Rohon-Beard sensory neurons. Both neural crest cells and Rohon- Beard sensory neurons arise from the lateral portion of the neural plate and while neural crest cells migrate extensively to form all of the peripheral nervous system (PNS; among other derivatives), Rohon-Beard sensory neurons remain within the central nervous system (CNS). The specific objective of this application is to determine the location of the progenitor population for neural crest and RB sensory neurons, to determine whether prdml actively regulates cell proliferation and/or differentiation of neural crest and RB sensory neurons and to identify the components of the molecular pathway of prdml regulation on border cell fates. Our hypothesis is that prdml is crucial for formation of neural crest and RB sensory neurons at the lateral neural plate. A series of experiments to test this hypothesis is proposed. We propose to test the hypothesis that neural plate border progenitors are spatially segregated and restricted in their innate cell competence and their ability to respond to the environment. In addition, we will test the hypothesis that prdml acts to specify cell fate by promoting the differentiation of precursor cells at the neural plate border, without affecting cell proliferation or cell death. Lastly, we will address the hypothesis that prdml acts as a transcriptional represser to repress the target genes required for the maintenance of the precursor fate and thus promoting differentiation. Towards these goals, we will take advantage of the zebrafish system, Danio rerio, because it has well-established experimental and genetic methods make a detailed analysis of this process feasible. As an outcome of these studies, it is expected to determine that the prdml transcription factor plays critical role in the specification of neural tube and crest cells. This will be important in determining the genetic pathways that are important for neural tube and crest development, which in turn will be an important step in preventative measures in human congenital defects, such as spinal bifida and cleft lip and palate.