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，人们对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，将探讨BMP信号复合物的性质，其在原肠胚形成期间起作用以使组织沿着脊椎动物背腹轴形成图案。长期的目标是了解多个配体和受体的要求，以BMP信号转导的分子基础。第二，我们将研究背腹轴和前后轴的图案形成沿着的协调性，检验这两个轴的图案形成是协调的这一假设。据推测，这种坐标图案化导致BMP活性随着时间的推移沿着前后轴逐渐作用以图案化背腹组织。最后，一个新的隐性背侧，母效应突变基因的分子性质和贡献，将进行研究，最大限度地提高我们的理解BMP信号在发展和疾病的遗传调控，通过功能丧失的研究。因此，识别和研究这一过程中的所有遗传参与者至关重要。 公共卫生相关性：骨形态发生蛋白（BMP）和TGF 2家族分泌的信号分子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。正在进行的研究表明，BMP和TGF 2信号转导在治疗各种疾病如肾病、肺动脉高压、胰腺癌、结肠直肠癌和其他癌症中的潜力，以及在医疗应用如整形外科、牙髓病学和组织工程中的潜力。我们了解BMP和TGF-2信号在发育和疾病中的生理作用，需要彻底研究它们的信号在无数生物学背景下产生不同细胞反应的手段，如本文所述。

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.