Protein /Nucleic Acid Interactions In Embryogenesis

在脊椎动物中，外胚层在原肠形成过程中被细分为四个主要命运：分别位于腹面和背面的表皮和中枢神经系统(CNS)，以及位于这两个区域之间的神经脊和感觉安慰剂。这个项目的目标是了解决定外胚层细胞如何在这些途径之间选择的机制，以及随后的组织图案和分化是如何受到调控的。这个实验室采取的实验方法是使用细胞-细胞信号的依赖性作为识别可能调节外胚层发育程序的基因的标准。人们的注意力集中在转录激活因子AP-2pha上。非洲爪哇神经隆起的诱导需要两个信号，一个是部分衰减的BMP信号，另一个是Wnt/β连接素信号。我们已经发现，AP2α负责将BMP信号传递到基因组，并激活广泛的神经峰特异性基因。AP2α在表皮发育过程中也起着至关重要的作用。 我们使用激素诱导版本的AP2pha作为工具，结合微阵列分析来识别表皮和神经脊中的靶基因。目前已鉴定出约100个这样的基因，其中许多具有已知的功能，如转录因子、信号分子、细胞外基质相关酶和其他结构或酶功能。许多基因也没有已知的功能，但在老鼠和人类的基因组中保守，因此很可能是重要的。我们现在的研究重点是确定这些基因中的一小部分的功能。特别是，我们对两个感兴趣；一个是我们命名为“Inca”的基因(AP2在神经峰中诱导的意思)。印加在青蛙、老鼠和斑马鱼中的序列和表达模式是保守的。在青蛙中，印加是头面部软骨和骨骼、肠道以及其他涉及神经脊的组织正常发育所必需的。另一个基因编码一种黏附分子，这种黏附分子在神经脊和发育中的体节中瞬时表达。此外，我们还在继续研究AP2转录因子家族及其在外胚层发育中的作用。由于这些基因在整个脊椎动物系统发育过程中都是保守的，我们的发现应该对生物医学研究和人类健康和发育具有广泛的相关性。

In vertebrates, the ectoderm is subdivided during gastrulation into four primary fates: epidermis and central nervous system (CNS) on the ventral and dorsal surfaces, respectively, and neural crest and sensory placodes located between these two domains. The goal of this project is to understand the mechanisms that determine how ectodermal cells choose between these pathways, and how the ensuing tissue patterning and differentiation are regulated. The experimental approach taken by this laboratory has been to use dependence upon cell-cell signaling as a criterion for identifying genes that may regulate the ectodermal developmental programs. Attention has been focused on the transcriptional activator AP-2alpha. Neural crest induction in Xenopus requires two signals, a partially attenuated BMP signal and a Wnt/beta catenin signal. We have found that AP2alpha is responsible for conveying the BMP signal to the genome, and activation of a broad spectrum of neural crest-specific genes. AP2alpha is also critical in the development of epidermis. We used a hormone-inducible version of AP2alpha as a tool in conjunction with microarray analysis to identifiy target genes in both epidermis and neural crest. Approximately 100 such genes have now been identified, many of which have known functions such as transcription factors, signaling molecules, extracellular matrix-related enzymes and other structural or enzymatic functions. Many also have no known function, but are conserved in the mouse and human genomes and are thus likely to be important. We are now focusing our research on determining the function of a small number of these genes. In particular, we are interested in two; one is a gene we named "Inca" (for Induced in Neural Crest by AP2). Inca is conserved in sequence and expression pattern in frogs, mice, and zebrafish. In the frog, Inca is required for proper development of the craniofacial cartilage and bones, the intestines, and other tissues where neural crest is involved. Another gene encodes an adhesion molecule that is transiently expressed in neural crest and developing somites. In addition we are continuing to study the AP2 family of transcription factors and their role in ectodermal development. Since these genes are conserved throughout vertebrate phylogeny, our findings should have broad relevance to biomedical research and human health and development.