Dorsal-Ventral Pattern Formation in the Zebrafish Embryo

描述（由申请人提供）：骨形态发生蛋白（BMP）家族的分泌信号分子在胚胎发生的不同阶段指导多种器官和组织类型的发育，并与先天性和成人疾病有关。通过对模式生物的研究，我们对BMP信号的生理作用有了深入的了解，这极大地增强了我们对人类发育和疾病的理解。在这里，BMP信号复合物的性质将被探讨，在原肠形成过程中，沿着脊椎动物的背-腹轴模式组织的功能。长期目标是了解多种配体和受体转导BMP信号的分子基础。其次，将研究沿背腹轴和前后轴的图案协调，测试这两个轴的图案是协调的假设。据推测，这种协调模式导致BMP活动随着时间的推移，沿着前后轴逐渐作用于背腹组织。最后，我们将研究一种新的隐性背化、母系效应突变基因的分子性质和作用，通过功能丧失研究，最大限度地了解BMP信号在发育和疾病中的遗传调控。因此，识别和研究这一过程中的所有基因参与者是至关重要的。

DESCRIPTION (provided by applicant): The Bone Morphogenetic Protein (BMP) family of secreted signaling molecules directs the development of multiple organs and tissue types at various stages in embryogenesis, and is implicated in congenital and adult diseases. Enormous insights into the physiologic roles of BMP signaling have been gained through their study in model organisms, which have vastly enhanced our understanding of human development and disease. Here the nature of the BMP signaling complex will be explored that functions during gastrulation to pattern tissues along the vertebrate dorsal- ventral axis. The long-term goal is to understand the molecular basis for the requirement for multiple ligands and receptors to transduce BMP signaling. Second the coordination of patterning along the dorsal-ventral and anterior-posterior axes will be investigated, testing the hypothesis that patterning of these two axes is coordinated. It is postulated that this coordinate patterning results in BMP activity acting progressively over time along the anterior-posterior axis to pattern dorsal-ventral tissues. Lastly, the molecular nature and contributions of a new recessive dorsalized, maternal-effect mutant gene, will be studied, to maximize our understanding of the genetic regulation of BMP signaling in development and disease through loss-of-function studies. Thus it is critical to identify and study all the genetic players in this process. Public Health Relevance: The Bone Morphogenetic Protein (BMP) and TGF2 family of secreted signaling molecules directs the development of multiple organs and tissue types and is implicated in congenital and adult diseases. Ongoing investigations suggest the potential for modulating BMP and TGF2 signaling in the treatment of disorders as diverse as kidney disease, pulmonary hypertension, pancreatic, colorectal, and other cancers, and in medical applications such as orthopedics, endodontics, and tissue engineering. Our understanding of the physiologic roles of BMP and TGF2 signaling in development and disease requires thorough studies of the means by which their signaling generates diverse cellular responses in a myriad of biological contexts, as will be studied here.