Dissecting the molecular mechanisms driving cell migration during neurulation triggered by the netrin receptor, neogenin

在人类中，在早期胚胎发育过程中大脑和脊髓形成的异常导致先天性综合征，如脊柱裂和无脑畸形。这些缺陷的发生率为1-1000例妊娠，因此是产前和围产期死亡的主要原因。在早期胚胎中，大脑和脊髓开始是一个中空的细胞管（神经管），随后扩展成出生时看到的复杂结构。众所周知，神经管是由一个复杂的过程形成的，在这个过程中，早期的神经细胞向胚胎的中线迁移，随后合并。该项目旨在确定一种分子信号通路（再生蛋白通路）的功能，该通路与驱动这些细胞迁移事件有关。我们将首先使用青蛙，非洲爪蟾，作为我们的胚胎模型，因为非洲爪蟾神经管的发育过程形成密切平行于那些发生在人类胚胎。这个模型将使我们能够识别再生蛋白信号通路中的分子。我们还将创造出携带再生蛋白基因突变的小鼠，这样我们就可以研究再生蛋白在哺乳动物中的功能。我们预计，这些研究将提供重要的见解，中枢神经系统的发展，也到异常的分子过程的神经管缺陷的人。

In humans, abnormalities in brain and spinal cord formation during early embryogenesis result in congenital syndromes such as spina bifida and anencephaly. These defects occur at a rate of 1-1000 pregnancies and are therefore a major contributor to pre- and perinatal deaths. In the early embryo, the brain and spinal cord begin as a hollow tube of cells (the neural tube) that subsequently expands into the complex structures seen at birth. It is known that the neural tube is formed by a complex process in which early neural cells migrate toward the midline of the embryo and subsequently coalesce. This project seeks to determine the function of one molecular signaling pathway (the neogenin pathway) that has been implicated in driving these cell migration events. We will initially use the frog, Xenopus laevis, as our embryonic model since the developmental processes that form the Xenopus neural tube closely parallel those ocurring in the human embryo. This model will allow us to identify the molecules in the neogenin signaling pathway. We will also create mice that carry a mutation in the neogenin gene so that we can study neogenin function in the mammal. We anticipate that these studies will provide important insights into the development of the central nervous system and also into the aberrant molecular processes underlying neural tube defects in man.