PROTEIN/NUCLEIC ACID INTERACTIONS IN VERTEBRATE EMBRYOGENESIS

脊椎动物和其他动物一样，外胚层有两个主要的功能：表皮和中枢神经系统（CNS）。该项目的目标是了解决定外胚层细胞如何在这两种途径之间选择的机制，以及随后的组织模式和分化是如何被调节的。实验室的主要重点是同源结构域基因Distal-less-3 （Dlx3）在这些过程中的功能。Dlx3在原肠期早期开始在外胚层表达。在神经管阶段，Dlx3的表达主要局限于表皮，在那里它在动物的整个生命中继续转录。然而，在原肠胚形成的早期到中期，当神经外胚层的初始模式发生时，Dlx3基因在未来神经板的前部区域短暂表达。这种表达是重要的，因为Dlx3可以作为神经特异性基因子集的负调节因子，包括在控制早期中枢神经系统分化中很重要的基因。Dlx3的原肠期表达域与另一个抗神经同源结构域基因Msx1部分重叠，Dlx3的转录延伸比Msx1更后。我们还发现Msx1选择性地阻断神经特异性基因的一个子集，其模式与Dlx3互补，并且Msx1和Dlx3对被认为调节发育中的外胚层组织特性的诱导分子（BMPs）表现出不同的敏感性。我们的结论是，这两个转录因子共同将一个或多个胚胎背化信号翻译成前神经板的初始空间模式。在接下来的一年里，实验室将专注于识别表皮的其他调节因子，部分通过研究先前报道的具有前表皮功能的基因，也通过进行减法和DNA序列分析筛选来识别具有这种特性的新因素。我们还将开展旨在阐明Dlx3抑制神经发育的机制的实验。-表皮，非洲爪蟾，神经发育，远端，Dlx3, Msx1

In vertebrates, as in other animals, the ectoderm has two primary fates, epidermis and central nervous system (CNS). The goal of this project is to understand the mechanisms that determine how ectodermal cells choose between these two pathways, and how the ensuing tissue patterning and differentiation are regulated. The main focus of the laboratory has been on the function of a homeodomain gene, Distal-less-3 (Dlx3), in these processes. Dlx3 is expressed in the ectoderm beginning at the early gastrula stage. By the neural tube stage Dlx3 expression is predominantly limited to the epidermis where it continues to be transcribed throughout the life of the animal. However, during early to mid- gastrulation, when the initial patterning of the neuroectoderm is taking place, the Dlx3 gene is transiently expressed in the anterior region of the future neural plate. This expression is significant because Dlx3 can act as a negative regulator of a subset of neural-specific genes, including that are important in the control of early CNS differentiation. The gastrula- stage expression domain of Dlx3 overlaps partially with that of another antineural homeodomain gene, Msx1, with Dlx3 transcription extending more posteriorly than that of Msx1. We have also found that Msx1 selectively blocks a subset of neural-specific genes, in a pattern complementary to that of Dlx3, and that Msx1 and Dlx3 exhibit differential sensitivity to inducer molecules (BMPs) that are thought to regulate tissue identity in the developing ectoderm. We conclude that these two transcription factors collaborate to translate one or more embryonic dorsalizing signals into an initial spatial pattern of the anterior neural plate. In the coming year, the lab will focus on identifying other regulators of epidermis, partly by investigating genes that have previously been reported to have pro-epidermal function, and also by carrying out a subtractive and DNA sequence analysis screen to identify novel factors with this property. We will also carry out experiments aimed at elucidating the mechanism by which Dlx3 can inhibit neural development. - epidermis, Xenopus laevis, neural development, Distal-less, Dlx3, Msx1