Signaling Mechanisms in the Crustacean Molting Gland

甲壳类动物的生长需要定期脱落外壳，这一过程称为蜕皮，由眼柄中的内分泌中心控制。该中心分泌两种肽类激素，蜕皮抑制激素（MIH）和甲壳类高血糖激素（CHH），它们抑制位于体内的一对蜕皮腺（Y器官或YOs）。正是YO，当被MIH的下降激活时，产生蜕皮所需的激素（蜕皮激素）。蜕皮过程的协调涉及YO和眼柄内分泌中心之间复杂的相互作用，这是知之甚少。据认为，MIH和CHH与膜受体的结合激活了单独的信号传导途径，这些信号传导途径会聚在产生蜕皮类固醇的酶的环核苷酸依赖性抑制上。YO是一个动态的组织，对不断变化的激素条件做出反应。因此，YO对激素信号的整合最终决定了动物何时蜕皮。使用比较的方法，结合了各种生化和分子技术，该项目将确定MIH和CHH信号通路的组成部分，以及蜕皮和肢体再生如何影响YO对MIH和CHH的敏感性。了解甲壳类动物蜕皮和生长的激素调节对于管理渔业、制定有效的水产养殖做法和减轻内分泌干扰物等污染物的潜在影响至关重要。尽管付出了巨大的努力，但人们对蜕皮腺对不同激素刺激的反应知之甚少。现在，表达大量活性MIH和CHH的方法是可用的，可以阐明信号通路，并可以确定与其他激素和污染物的潜在相互作用。一氧化氮在MIH信号传导中的潜在作用构成了一个全新的和令人兴奋的研究方向。该项目将培养一名博士后研究员，两名研究生和四名本科生先进分子生物学技术。

Growth in crustaceans requires the periodic shedding of the shell, a process called molting, which is controlled by an endocrine center in the eyestalks. The center secretes two peptide hormones, molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone (CHH), which inhibit a pair of molting glands (Y-organs or YOs) located in the body. It is the YO, when activated by a drop in MIH, that makes the hormone (ecdysteroid) required for molting. Coordination of molting processes involves a complex interaction between the YO and the eyestalk endocrine center that is poorly understood. It is thought that binding of MIH and CHH to membrane receptors activates separate signaling pathways that converge at cyclic nucleotide-dependent inhibition of enzymes that make ecdysteroid. The YO is a dynamic tissue responsive to changing hormonal conditions. Thus, it is the integration of the hormonal signals by the YO that ultimately determines when an animal molts. Using a comparative approach that incorporates a variety of biochemical and molecular techniques, the project will determine the components of the MIH and CHH signaling pathways and how molting and limb regeneration affect YO sensitivity to MIH and CHH. Understanding the hormonal regulation of crustacean molting and growth is essential to manage fisheries, develop effective aquaculture practices, and mitigate potential effects of pollutants, such as endocrine disruptors. Despite intense effort, very little is known about the molting gland responds to varying hormonal stimuli. Now that methods to express large amounts of active MIH and CHH are available, the signaling pathways can be elucidated and potential interactions with other hormones and pollutants can be determined. The potential role of nitric oxide in MIH signaling constitutes an entirely novel and exciting line of investigation. The project will train a postdoctoral fellow, two graduate students, and four undergraduates in advanced molecular biological techniques.