Activin receptor patterning of foregut organogenesis

Foregut development produces a characteristic sequence of gastrointestinal and respiratory organs, but the signaling pathways that ensure this develop mental order remain largely unknown. Here, mutations of activin receptors A ctRIIA and ActRIIB are shown to disrupt the development of posterior foregu t-derived organs, including the stomach, pancreas, and spleen. Foregut expr ession of genes including Shh and Isl1 is shifted in mutant mice. The endoc rine pancreas is particularly sensitive to the type and extent of receptor inactivation. ActRIIA(+/-)B(+/-)animals lack axial defects, but have hypopl astic pancreatic islets, hypoinsulinemia, and impaired glucose tolerance. T hus, activin receptor-mediated signaling regulates axial patterning, cell d ifferentiation, and function of foregut-derived organs.