Endocrine Regulation of Stomach Organogenesis

University Of Rhode Island, Kingston RI

Investigators

Abstract

The stomach is an important organ, both physiologically and ecologically. From a comparative perspective, the structure and function of the stomach are similar across vertebrate classes, whereas the timing of its formation in the life cycle is variable. Little is known about the endocrine regulation of stomach organogenesis. In vertebrates, corticosteroids and thyroid hormones significantly regulate development, however their metabolic functions in adults are more thoroughly studied. The larger idea here is that these are the hormones that connect metabolism and metabolic state with growth and development. The proposed project tests the hypothesis that stomach organogenesis is regulated by sequential action of cortisol and thyroid hormones on cell proliferation and differentiation. The endocrine regulation of organogenesis is more easily studied in free-living larval stages than in embryonic/fetal stages because of the ease of manipulation of hormone levels. The experimental animal used to test this hypothesis is the marine flatfish summer flounder (Paralichthys dentatus). In summer flounder, stomach organogenesis occurs at the end of the larval phase during metamorphosis. Metamorphosing flounder can be staged based on the translocation of the right eye to the left side of the head (like the hand on a clock). This permits stage-specific experimentation that is difficult or impossible otherwise. In the incipient stomach, the developmental progression of proliferation, morphogenesis, and cell differentiation is closely associated with sequential amplification of corticosteroid and thyroid hormone signalling. These hormones act through intracellular receptors that serve as transcription factors. How do these hormones coordinate the cellular and intercellular mechanisms of organogenesis? The research plan integrates responses at the organismal, organ, tissue, and cellular and molecular levels of organization. End-points are morphogenesis, morphometrics, cell proliferation and differentiation, hormone concentrations, and quantification and localization of the receptors for cortisol and thyroid hormones. The broad significance of the award includes the research training of early scientists, possible contributions to the development of aquaculture of marine fishes, and basic understanding of the endocrine regulation of cellular proliferation and differentiation.