Dividing the tubular gut: Generation of organ boundaries at the pylorus

The discrete organs that comprise the gastrointestinal tract (esophagus, stomach, small intestine, and large intestine) arise embryonically by regional differentiation of a single tube that is initially morphologically similar along its length. Regional organ differentiation programs, for example, for stomach or intestine, involve signaling cross-talk between epithelium and mesenchyme and result in the formation of precise boundaries between organs, across which dramatic differences in both morphology and gene expression are seen. The pylorus is a unique area of the gut tube because it not only marks an important organ boundary in the tubular gut (the stomach/intestinal boundary) but is also the hub for the development of multiple accessory organs (liver, pancreas, gall bladder, and spleen). This chapter examines: (a) our current understanding of the molecular and morphogenic processes that underlie the generation of the dramatic epithelial tissue boundary that compartmentalizes stomach and intestine; (b) the tissue interactions that promote development of the accessory organs in this area; and (c) the molecular interactions that specify patterning of the pyloric sphincter. Though the focus here is primarily on the mouse as a model organism, the molecular underpinnings of organ patterning near the pylorus are shared by chick and frog. Thus, further study of these conserved developmental programs could potentially shed light on the mechanisms underlying human pyloric malformations such as infantile hypertrophic pyloric stenosis.