Tissue interactions and morphogenesis at the midline during vertebrate development

在脊椎动物的早期发育过程中，构成中线结构的组织对随后的形态发生起着重要的作用。我之前发现神经管和它上面的表面外胚层相互作用。异位移植的神经管诱导了同源框基因MSX-2在移植部位的表面外胚层中表达。这项研究项目的目的是揭示调控这些相互作用的分子机制1。神经管与皮肤相互作用的分子本质我发现，在神经管的背部表达的BMP-4家族成员BMP-4作用于神经管上覆的皮肤，使其表达MSX-2。将转BMP-4基因的COS细胞植入异位区，这种操作在植入部位诱导了MSX-2的表达。2.BMP-4在腹侧区域的作用。除了BMP-4在神经管中的作用外，我还发现BMP-4似乎在身体腹侧区域的形成中起到了一定的作用。当高浓度的BMP-4注射到背侧中胚层时，该区域完全转化为腹侧中胚层。利用各种分子标记揭示了这一现象。从这些结果看，BMP-4不仅在背中线起作用，而且在身体腹侧组织的形态发生中也起作用。有趣的是，这两个组织都位于远离脊索的地方。因此，可以想象，脊索发出的因子与BMP-4相互抵消，而这些相互作用控制着复杂的形态发生。

During early development in vertebrate, tissues constituting the midline structures play important plays for subsequent morphogenesis. I previously found that the neural tube and its overlying surface ectoderm interact each other. It was shown by the fact that an ectopically transplanted neural tube induced expression of a homeobox gene, Msx 2, in the surface ectoderm at the graft site. The aim of this research project was to unveil the molecular mechanisms by which these interactions are regulated.1. Molecular nature of interactions acting between the neural tube and the skin.I found that BMP-4, a member of TGFbeta family, which is expressed in the dorsal portion of the neural tube acts on the overlying skin to cause it to express Msx 2. COS cells which had been transfected with BMP-4 cDNA were implanted into an ectopic region and this manipulation induced Msx 2 expression at the implantation site.2.Role of BMP-4 in the ventral region.In addition to the roles of BMP-4 in the neural tube, I also found that BMP-4 appears to have some roles in the formation of the ventral region of the body. When a high concentration of BMP-4 was administered into the dorsal mesoderm, this region was completely converted to the ventral mesoderm. It was revealed by using various molecular markers. Moreover, these effects were concentration-dependent.From these results, BMP-4 appears to play roles not only at the dorsal midline but also in the morphogenesis of the ventral tissues of the body. Interestingly, both tissues are located far from the notochord. Therefore, it is conceivable that factors emanating form the notochord counteract with BMP-4, and that these counteractions control complex morphogenesis.