Barx1-Mediated Inhibition of Wnt Signaling in the Mouse Thoracic Foregut Controls Tracheo-Esophageal Septation and Epithelial Differentiation

• DOI: 10.1371/journal.pone.0022493
• Publication Date: 2011-07-22T19:01:29Z
• Authors: Janghee Woo; Isabelle Miletich; Byeong-Moo Kim; Paul T. Sharpe; Ramesh A. Shivdasani
• Keywords: Foregut; Mesenchyme

Mesenchymal cells underlying the definitive endoderm in vertebrate animals play a vital role digestive and respiratory organogenesis. Although several signaling pathways are implicated foregut patterning morphogenesis, despite clinical importance of congenital tracheal esophageal malformations humans, understanding molecular mechanisms that allow single tube to separate correctly into trachea esophagus is incomplete. The homoebox gene Barx1 highly expressed prospective stomach mesenchyme required specify this organ. We observed lower expression extending contiguously from proximal domain, along dorsal anterior mesenchymal between nascent trachea. This pattern exactly mirrors decline Wnt activity late development adjacent medial mainstem bronchi. hypopharynx Barx1−/− mouse embryos abnormally elongated point esophago-tracheal separation shows marked caudal displacement, resulting common similar human tracheo-esophageal fistula explains neonatal lethality. Moreover, displays cytologic features endoderm, phenocopying abnormalities with activated ß-catenin. zone canonical prolonged expanded foregut. Thus, as developing stomach, but distinct spleen, control thoracic specification septation tightly associated down-regulation pathway activity.