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Developmental disorders of the esophagus are relatively common, occurring in approximately 1 in 3000 live births. Because of the shared embryologic origins of the esophagus and respiratory system, esophageal defects commonly correlate with concurrent defects in the lungs and trachea. These defects include several combinations of esophageal atresia and tracheoesophageal fistula. The defects, understandably, can lead to difficulties with feeding and, in some cases maintaining oxygenation, requiring urgent attention in the perinatal period. In utero, defects of the esophagus can lead to difficult birth conditions stemming from the decreased ability to swallow and resultant polyhydramnios. While the process of organogenesis is immensely complex and the cellular mediators are still being worked out, a basic understanding of the current knowledge on esophageal embryology is important for understanding the link between congenital esophageal and tracheal malformations.

Researchers have identified various Tracheoesophageal Fistula (TE) malformations by altering the gene regulation in knockout mice. These include: Regulatory mediator Noggin, produced by the notochord, mediates continued specification and differentiation of the respiratory system from the foregut. Studies in mice highlight this regulatory role, where disruption of the notochord resulted in tracheal-esophageal fistulas and esophageal atresia with excessive endodermal tissue. Wnt5a-Ror2 signaling plays a critical role in elongation for the trachea and esophagus. The knockout of wnt5a in mice has shown truncated esophagus development. Sonic hedgehog (Shh) has a critical role in the development of the esophagus and other structures. Studies of Shh knock out mice show decreased rates of cell division and transcription factor expression.[18] Decreased Shh expression has also been associated with lung hypoplasia, abnormalities in smooth muscle migration, esophageal atresia, and stenosis, indicating the important regulatory roles for this protein in the development of the esophagus and suggesting important roles in human foregut defects.[2][11] Briefly, various other factors resulting in esophageal malformations are as following: P63 knockout mice show disruption in the stratification of squamous epithelium.[2] Loss of  Keap1 results in thick keratinization in the esophagus.[2] Lastly, knockout HoxC4 results in an obliterated esophageal lumen from over-proliferation, implying a suppression effect of HoxC4.[2]