Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut boundary

Patterning of the gut into morphologically distinct regions results from th e appropriate factors being expressed in strict spatial and temporal patter ns to assign cells their fates in development. Often, the boundaries of gen e expression early in development correspond to delineations between differ ent regions of the adult gut. For example, Bmp4 is expressed throughout the hindgut and midgut, but is not expressed in the early gizzard, Ectopic BMP 4 in the gizzard caused a thinning of the muscularis. To understand this ph enotype we examined the expression of the receptors transducing BMP signali ng during gut development. We find that the BMP receptors are differentiall y expressed in distinct regions of the chicken embryonic gut. By using cons titutively activated versions of the BMP type I receptors, we find that the BMP receptors act similarly to BMP4 in the gizzard when ectopically expres sed. We show that the mesodermal thinning seen upon ectopic BMP signaling i s due to an increase in apoptosis and a decrease in proliferation within th e gizzard mesoderm, The mesodermal thinning is characterized by a disorgani zation and lack of differentiation of smooth muscle in the gizzard mesoderm . Further, ectopic BMP receptors cause an upregulation of Nkx2.5, the pylor ic sphincter marker, similar to that seen with ectopic BMP4. This upregulat ion of Nkx2.5 is a cell-autonomous event within the mesoderm of the gizzard , We also find that Nkx2.5 is necessary and sufficient for establishing asp ects of pyloric sphincter differentiation.