barx1-mediated inhibition of wnt signaling in the mouse thoracic foregut controls tracheo-esophageal septation and epithelial differentiation胸barx1-mediated抑制wnt信号在鼠标前肠控制气管食管分隔作用和上皮分化.pdfVIP

Barx1-Mediated Inhibition of Wnt Signaling in the Mouse Thoracic Foregut Controls Tracheo-Esophageal Septation and Epithelial Differentiation 1,2 3 1 3 1,4 Janghee Woo , Isabelle Miletich , Byeong-Moo Kim , Paul T. Sharpe , Ramesh A. Shivdasani * 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America, 2 Graduate Program in Biological and Biomedical Science, Harvard University, Cambridge, Massachusetts, United States of America, 3 Department of Craniofacial Development, Dental Institute, King’s College, London, United Kingdom, 4 Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America Abstract Mesenchymal cells underlying the definitive endoderm in vertebrate animals play a vital role in digestive and respiratory organogenesis. Although several signaling pathways are implicated in foregut patterning and morphogenesis, and despite the clinical importance of congenital tracheal and esophageal malformations in humans, understanding of molecular mechanisms that allow a single tube to separate correctly into the trachea and esophagus is incomplete. The homoebox gene Barx1 is highly expressed in prospective stomach mesenchyme and required to specify this organ. We observed lower Barx1 expression extending contiguously from the proximal stomach domain, along the dorsal anterior foregut mesenchyme and in mesenchymal cells between the nascent esophagus and trachea. This expression pattern exactly mirrors the decline in Wnt signaling activity in late development of the adjacent dorsal foregut endoderm and