Neuroendocrine Control of Amphibian Metamorphosis

发育中的动物通过改变它们的发育速率和/或它们的形态来响应它们栖息地的变化;即，它们表现出发育可塑性。表达可塑性的一种机制是通过激活神经内分泌系统，将环境信息转换为生理反应。我们最近对两栖动物和其他哺乳动物的研究结果表明，脊椎动物的主要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依赖性机制导致某些两栖动物物种对栖息地干燥应激的加速变态，人类的宫内胎儿应激综合征导致早产。该研究的目的是分析脊椎动物发育过程中CRH信号传导的细胞和分子机制。南非爪蟾的蝌蚪将被用作模式生物。这些研究的结果将提供基本信息的分子和功能组织的这一重要的发展监管系统。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允许更知情和详细的了解正常的内分泌控制途径，知识，将是必不可少的阐明环境内分泌干扰物的作用，以改变发育过程的机制。考虑到最近关于两栖动物种群在全球范围内下降的报道以及对激素模拟工业化合物对人类和野生动物发育影响的担忧，这样一个目标尤其令人信服。

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.