Molecular Embryology of the Foregut

Abstract

The digestive and respiratory systems have different physiological functions (nutrition, food transit and evacuation for the first; breathing and oxygen supply to the blood for the second) and are generally considered and studied as two independent structures. Nevertheless, although at birth they are separated, they both derive from a common and transient developmental structure, the foregut, which is the anterior part of the gastrointestinal (GI) tract (1). The GI tract is a remarkably complex, three-dimensional, specialized and vital system that is derived from a simple tube-like structure. The vertebrate GI tract includes the luminal digestive system (i.e., esophagus, stomach, intestine and colon, which we will designate on the whole as “gut”) and the GI-tract derivatives (i.e., thyroid, lungs, liver and pancreas). The gut is composed of three germ layers: mesoderm (which forms the smooth muscle layer), endoderm (which forms the epithelial lining) and ectoderm (which includes the enteric nervous system). The gut develops from two invaginations at the anterior (anterior intestinal portal, AIP) and posterior (caudal intestinal portal, CIP) end of the embryo that elongate and fuse to form a straight tube. The primitive gut tube is initially patterned into three broad domains along its anterior-posterior (AP) axis: the fore-, mid- and hindgut. As they develop, each region of the gut is characterized by unique mesodermal and endodermal morphologies, which can easily be discerned by gross and microscopic examination. Specifically, these tissues show regional differentiation along the AP axis that specifies pharynx, esophagus and stomach (the foregut), small intestine (the midgut) and large intestine (hindgut). This regionalization is maintained throughout life and is essential and necessary for normal gut function. These patterning events are remarkably conserved across species (1) and patterning anomalies are likely to be responsible for many of the human gut malformation syndromes, such as tracheo-esophageal atresia (TE), infantile hypertrophic pyloric stenosis or anal atresia (1,2).