Although the gut is homologous among different vertebrates, morphological d
ifferences exist between different species. The most obvious variation in t
he guts of extant vertebrates appears in the stomach. To investigate the ev
olution of this structure, we compared the histology of the stomach and gas
trointestinal tract in amphibian (Xenopus laevis), avian (Gallus gallus), a
nd mammalian (Mus musculus) organisms, and defined the expression patterns
of several genes within the developing guts of these lineages. In all three
groups, we find that the anterior portion of the stomach has a similar gla
ndular histology as well as a common embryonic expression of the secreted f
actors Wnt5a and BMP-4. Likewise, within the amniote lineages, the posterio
r nonglandular stomach and pyloric sphincter regions are also comparable in
both histological and molecular phenotypes. The posterior stomach expresse
s Six2, BMPR1B, and Barx1, whereas the pyloric sphincter expresses Nkx2.5.
Although the adult Xenopus stomach exhibits both glandular and aglandular r
egions and a distinct pyloric sphincter similar to that of the amniotic ver
tebrates, the histology of the Xenopus tadpole gut shows less distinct vari
ation in differentiation in this region, which is most likely a derived con
dition. The molecular signature of the embryonic Xenopus gut correlates wit
h the more derived morphology of the larval phase. We conclude that the glo
bal patterning of the gut is remarkably similar among the different vertebr
ate lineages. The distinct compartments of gene expression that we find in
the gut be necessary for the unique morphological specializations that dist
inguish the stomachs from terrestrial vertebrates.