R. Douglas Watson
Professor, Endocrinology & Developmental Biology
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 cell soma 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 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 postembryonic 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.
Han, D.-W., Patel, N. and Watson, R.D. (2006) Regulation of protein synthesis in Y-organs of the blue crab (Callinectes sapidus): Involvement of cyclic AMP. J. Exp. Zool. 305A:328-334.
Zheng, J., Lee, C.-Y. and Watson, R.D. (2006) Molecular cloning of a putative receptor guanylyl cyclase from Y-organs of the blue crab, Callinectes sapidus. Gen. Comp. Endocrinol. 146:329-336.
Nakatsuji, T., Sonobe, H., and Watson, R.D. (2006) Molt-inhibiting hormone-mediated regulation of ecdysteroid synthesis in Y-organs of the crayfish (Procambarus clarkii): involvement of cyclic GMP and cyclic nucleotide phosphodiesterase. Molec. Cell. Endocrinol. 253:76-83.
Nakatsuji, T., Han, D.-W., Jablonsky, M.J., Harville, S.R., Muccio, D.D., and Watson, R.D. (2006) Expression of crustacean (Callinectes sapidus) molt-inhibiting hormone in Escherichia coli: Characterization of the recombinant peptide and assessment of its effects on cellular signaling pathways in Y-organs. Molec. Cell. Endocrinol. 253:96-104.
Choi, C.Y., Zheng, J., and Watson, R.D. (2006) Molecular cloning of a cDNA encoding a crustacean hyperglycemic hormone from eyestalk ganglia of the blue crab, Callinectes sapidus. Gen. Comp. Endocrinol. 148:383-387.
Chen, H.-Y., Watson, R.D., Chen, J.-C., Liu, H.-F., and Lee, C.-Y. (2007) Molecular characterization and gene expression patterns of two putative molt-inhibiting hormones from Litopenaeus vannamei. Gen. Comp. Endocrinol. 151:72-81.
Zheng, J., Nakatsuji, T., Roer, R.D., and Watson, R.D. (2008) Studies of a receptor guanylyl cyclase cloned from Y-organs of the blue crab (Callinectes sapidus), and its possible functional link to ecdysteroidogenesis. Gen. Comp. Endocrinol. 155:780-788.
Nakatsuji, T., Lee, C.-Y., and Watson, R.D. (2009) Crustacean molt-inhibiting hormone: structure, function, and cellular mode of action. Comp. Biochem. Physiol. A 152:139-148.
Chang, C.-C., Tsai, K.-W., Hsiao, N.-W., Chang, C.-Y., Lin, C.-L., Watson, R.D., and Lee, C.-Y. (2010) Structural and functional comparisons and production of recombinant crustacean hyperglycemic hormone (CHH) and CHH-like peptides from the mud crab Scylla olivacea. Gen. Comp. Endocrinol. Gen. Comp. Endocrinol. 167:68-76.
Zheng, J., Chen, H.-Y., Choi, C.-Y., Roer, R.D., and Watson, R.D. (2010) Molecular cloning of a putative crustacean hyperglycemic hormone (CHH) isoform from extra-eyestalk tissue of the blue crab (Callinectes sapidus), and determination of temporal and spatial patterns of CHH gene expression. Gen. Comp. Endocrinol. 169:174-181.