PROGRAMS THAT DIFFERENTIATE PRESTRUCTURAL TISSUES

从前结构组织发育成复杂的器官是一种 神秘的过程转分化和器官特化依赖于 生物事件的相互作用，这些生物事件在组装过程中迅速移动， 胚胎发育中的结构-功能关系。细胞 分化是一个积极的过程，这表明在线的作用， 基因调控我们认为器官发育取决于 转录序列的参与和连续性 对形态发生线索作出反应的蛋白质。这些发展项目是 限制性的、决定性的并且通常是组织特异性的。很少有 这个监管难题是众所周知的，我们相信一个计划项目， 我们将在这一领域培养新的跨学科研究。的 在我们的计划组合项目共同桥梁学科， 遗传学和生物化学与基础病理生理学支持六个 建立了研究实验室， 发育生物学每个项目负责人都来自 多样化的职业道路，并带来特殊的互动优势， 更大的集团。我们所有的项目最初都集中在啮齿动物上。 项目1将确定新的Kruppel型锌指， 肾脏发育的早期阶段;项目2将侧重于比较 调节肝脏发育和调节的遗传程序;项目 3将研究连接蛋白43（Cx43）的扰动对 缝隙连接蛋白在分化过程中的表达 肾单位;项目4将评估叉头域在 在早期肾发生中有活性的转录因子;项目5 将确定在脂肪组织分化中重要的基因， 使用视黄酸作为形态发生剂来探测 前脂肪细胞;和项目6将检查尾- 在发育中的肠的内胚层中的相关同源结构域蛋白。核心 项目管理、分子生物学和胚胎学单位 组织化学将提供必要和适当的基础设施。 它 我们希望并期望我们的工作将成功地确定 一些重要的监管事件的位置坐标， 对早期器官发育中重要基因的深入研究。

The development of complex organs from pre-structural tissues is a mysterious process. Transdifferentiation and organ specialization depend on an interaction of biologic events which move rapidly in the assembly of structure-function relationships in the growing embryo. Cell differentiation is an active process and this suggests an on-line role for gene modulation. We believe that organ development depends on the participation and continuity of sequential sets of transcriptional proteins responding to morphogenic cues. Such developmental programs are restrictive, decisional, and usually tissue-specific. Very few pieces of this regulatory puzzle are known, and we believe a program project such as ours will cultivate new interdisciplinary research in this area. The projects in our program portfolio collectively bridge the disciplines of genetics and biochemistry with basic pathophysiology in support of six established research laboratories with common interest in the developmental biology of amniotes. Each of the project leaders come from diverse career pathways and bring special interactive strengths to the larger group. All of our projects are initially focused on rodents. Project 1 will identify new Kruppel-type zinc fingers expressed in the early stages of kidney development; Project 2 will focus on the comparison of genetic programs regulating hepatic development and regulation; Project 3 will investigate the effects of perturbations of Connexin 43 (Cx43) on the expression of gap junction proteins during the differentiation of nephrons; Project 4 will evaluate the role of forkhead domains in transcription factors that are active in early nephrogenesis; Project 5 will identify the genes important in the differentiation of adipose tissue using retinoic acid as a morphogen to probe the conversion of preadipocytes; and Project 6 will examine the molecular actions of caudal- related homeodomain proteins in the endoderm of developing intestine. Core units for project administration, molecular biology, and embryologic histochemistry will provide necessary and appropriate infrastructure. It is our hope and expectation that our work will successfully identify the positional coordinates for some important regulatory events by beginning an intensive study of significant genes in early organ development.