PROGRAMS THAT DIFFERENTIATE PRESTRUCTURAL TISSUES

从前结构组织到复杂器官的发育是一个 神秘的过程。转分化和器官特化取决于 关于生物事件在集合中快速移动的相互作用 发育中胚胎的结构-功能关系。细胞 差异化是一个积极的过程，这表明在线角色 基因调制。我们认为器官的发育取决于 转录序列集的参与性和连续性 对形态发生线索作出反应的蛋白质。这样的发展计划是 限制性的，决定性的，通常是组织特异性的。极少有几件 这个监管难题是已知的，我们相信像这样的项目 我们将在这一领域培养新的跨学科研究。这个 我们计划组合中的项目共同搭建了以下学科的桥梁 遗传学和生物化学与基础病理生理学相结合 建立了研究实验室，共同关心 羊膜的发育生物学。每个项目负责人都来自 多元化的职业道路，为员工带来独特的互动优势 更大的群体。我们所有的项目最初都专注于啮齿动物。 项目1将识别新的Kruppel类型的锌指，在 肾脏发育的早期阶段；项目2将侧重于比较 管理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 缝隙连接蛋白在鼻咽癌分化过程中的表达 项目4将评估叉头域在以下方面的作用 在早期肾脏形成中活跃的转录因子；项目5 将确定在脂肪组织分化中重要的基因 以维甲酸为成形剂，探索细胞的转化 前脂肪细胞；项目6将研究尾部- 发育中肠道内胚层中的相关同源结构域蛋白。堆芯 项目管理、分子生物学和胚胎学 组织化学将提供必要和适当的基础设施。它 就是我们希望和期待我们的工作能够成功地识别 一些重要监管事件的位置坐标通过开始 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.