Neural tube development

在大脑和脊髓发育的早期关键步骤是神经管关闭的机制。这就是将早期的大脑原基从扁平的细胞片转变为管状细胞的机制。然后，管状结构一直维持到成年。当胚胎发育过程出错时，就会导致神经管缺陷，如脊柱裂。我们最近发现，在斑马鱼胚胎中，这一过程依赖于一种新的细胞分裂模式，我们称之为镜像对称分裂。我们将研究哪些分子机制在调节这种新的细胞分裂模式中起重要作用。特别是，我们将专注于一种蛋白质，它在无脊椎动物胚胎发育中的作用强烈表明，它们可能有助于控制镜像对称分裂。我们还将研究这种分裂如何产生结合在一起的细胞，使管状结构得以发育。目前还不确定其他脊椎动物胚胎是否在大脑发育中使用这种特殊的分裂模式，但有一些理由相信青蛙胚胎和小鸡胚胎可以使用类似的过程。在这项工作中，我们将确定镜像对称分裂是否存在于早期青蛙和雏鸡胚胎神经管中。此外，我们将确定胚胎中也产生管状结构的其他部分(如肠道)是否也使用镜像对称分裂作为产生管状结构的一个步骤。

A key early step during development of the brain and spinal cord is the mechanism of neural tube closure. This is the mechanism that transforms the early brain primordium from a flat sheet of cells into a tube. The tubular structure is then maintained through to adulthood. When this embryonic process goes wrong, neural tube defects such as spina bifida result. We have recently discovered that in the zebrafish embryo this process depends on a novel mode of cell division, which we have termed mirror-symmetric division. We will investigate which molecular mechaisms are important in the regulation of this novel mode of cell division. In particular we will concentrate on a proteins whose role in the development of invertebrate embryos strongly suggest they could contribute to the control of mirror-symmetric divisions. We will also investigate how this division generates cells that are bound together in an arrangement that allows the tubular structure to develop. It is uncertain at present whether other vertebrate embryos employ this specialised mode of division in brain development, but there is some reason to believe that frog embryos and chick embryos could use a similar process. In this work we will determine whether mirror-symmetric divisions are present in the early frog and chick embryo neural tubes. In addition we will determine whether other parts of the embryo that also generate tubular structures (like the gut) also use mirror-symmetric division as a step in the generation of tubes.