My laboratory is studying the mechanisms by which hormones control development. Our research is multidisciplinary, drawing on the fields of molecular biology, biochemistry, and physiology. We are currently using two invertebrate models, the blue crab (Callinectes sapidus) and the crayfish (Procambarus clarkii). In crustaceans, cycles of growth and molting and associated developmental processes, including regeneration, are controlled by the endocrine system. The cellular events that lead to molting are stimulated by steroid hormones termed ecdysteroids. Ecdysteroids are secreted by paired Y-organs. The synthesis of ecdysteroids by Y-organs is negatively regulated (inhibited) by a polypeptide neurohormone, molt-inhibiting hormone (MIH). MIH is produced in a cluster of neurosecretory cells located in eyestalk neural ganglia. Our current projects include the following:
Cellular signaling pathways linked to regulation of ecdysteroid synthesis. We are studying the link of MIH receptor activation to cyclic nucleotide cellular signaling pathways in Y-organs. Our data indicate that cGMP is the second messenger directly linked to MIH action in Y-organs of both C. sapidus and P. clarkii. The catabolism of cGMP is catalyzed by cyclic nucleotide phosphodiesterases (PDEs). Our recent studies have begun to clarify the critical roles of PDEs in defining the magnitude and duration of the cGMP signal in Y-organs. Cellular signaling molecules other than cGMP have also been implicated, directly or indirectly, in MIH action. Among these, calcium appears to play a critical role. We are also currently investigating the roles of calcium signaling in regulation of ecdysteroidogenesis.
MIH receptor structure and function. Based on studies of cellular signaling in Y-organs, we hypothesize that the MIH receptor is a receptor guanylyl cyclase (rGC), and have cloned from Y-organs of C. sapidus a candidate MIH receptor. We are conducting experiments designed to assess the ability of MIH to bind and activate the candidate receptor, and to determine whether changes in MIH receptor number are responsible of developmental changes in the responsiveness of Y-organs to MIH.
From the standpoint of basic science, our research is focused on answering crucial questions regarding the endocrine regulation of development. From the standpoint of applied science, the findings may lead to development of methods for manipulating growth and molting, a potential benefit to fisheries managers, the aquaculture industry, and consumers.
Physiology of Endocrine and Neuroendocrine Systems; Regulation of Hormone Synthesis and Secretion; Cellular and Molecular Actions of Hormones on Target Tissues
