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。我以前发现，神经管和其上覆的外胚层相互作用。异位移植的神经管在移植部位的表面外胚层中诱导同源异型盒基因Msx 2的表达。本研究项目的目的是揭示调节这些相互作用的分子机制。神经管和皮肤之间相互作用的分子本质。我发现BMP-4是TGF β家族的一员，在神经管的背部表达，作用于覆盖的皮肤，使其表达Msx 2。将转染BMP-4 cDNA的COS细胞植入异位区，诱导Msx 2在植入部位表达。2. BMP-4在腹侧区的作用除了在神经管中的作用外，我还发现BMP-4似乎在身体腹侧区的形成中也有一些作用。当高浓度的BMP-4被注入背侧中胚层时，该区域完全转化为腹侧中胚层。通过多种分子标记的检测，揭示了该基因的多态性。从这些结果来看，BMP-4似乎不仅在背中线上起作用，而且在身体腹侧组织的形态发生中也起作用。有趣的是，这两种组织都远离脊索。因此，可以想象，从脊索发出的因子与BMP-4相互抵消，并且这些抵消作用控制复杂的形态发生。

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.