Neuroendocrine Control of Amphibian Metamorphosis

发育中的动物通过改变其发育速度和/或形态来应对栖息地的变化；也就是说，它们表现出发育可塑性。可塑性表达的一种机制是通过激活神经内分泌系统，将环境信息转化为生理反应。最近对两栖动物和哺乳动物的研究表明，初级脊椎动物应激神经肽促肾上腺皮质激素释放激素（CRH）对环境应激的适应性发育反应至关重要。例如，CRH依赖机制导致一些两栖动物在栖息地干燥胁迫下加速变态，而人类的宫内胎儿应激综合征会导致早产。本研究的目的是分析CRH信号在脊椎动物发育过程中的细胞和分子机制。南非爪蟾（Xenopus laevis）的蝌蚪将被用作模式生物。这些研究结果将为这一重要的发育调控系统的分子和功能组织提供基本信息。此外，这些研究应该为理解发育对物理和化学环境变化的反应的机制基础奠定基础。从这些研究中获得的基本知识应该使我们对内分泌控制的正常途径有更全面和详细的了解，这些知识对于阐明环境内分泌干扰物改变发育过程的机制至关重要。考虑到最近世界范围内两栖动物数量下降的报道，以及人们对模拟激素的工业化合物对人类和野生动物发育的影响的担忧，这样一个目标尤其有说服力。

Developing animals respond to variation in their habitat by altering their rate of development and/or their morphology; i.e., they exhibit developmental plasticity. One mechanism by which plasticity is expressed is through activation of the neuroendocrine system, which transduces environmental information into a physiological response. Recent findings of ours with amphibians and others with mammals show that the primary vertebrate stress neuropeptide, corticotropin-releasing hormone (CRH) is essential for adaptive developmental responses to environmental stress. For instance, CRH dependent mechanisms cause accelerated metamorphosis in response to habitat desiccation stress in some amphibian species, and intrauterine fetal stress syndromes in humans precipitate preterm birth. The objectives of the proposed research are to analyze the cellular and molecular mechanisms of CRH signaling during vertebrate development. Tadpoles of the South African clawed frog Xenopus laevis will be used as the model organism. The results of these studies will provide basic information on the molecular and functional organization of this essential developmental regulatory system. Furthermore, these studies should lay a foundation for understanding the mechanistic basis of developmental responses to changes in the physical and chemical environment. Basic knowledge gained from these studies should allow a more informed and detailed understanding of normal pathways of endocrine control, knowledge that will be essential to elucidating the mechanisms by which environmental endocrine disrupters act to alter developmental processes. Such a goal is particularly cogent given recent reports of worldwide declines in amphibian populations and concerns over the effects of hormone mimicking industrial compounds on the development of humans and wild animals.