Wnt9b-dependent FGF signaling is crucial for outgrowth of the nasal and maxillary processes during upper jaw and lip development

• Published in: Development (Cambridge) Vol. 139; no. 10; pp. 1821 - 1830
• Main Authors: Jin, Yong-Ri, Han, Xiang Hua, Taketo, Makoto M, Yoon, Jeong Kyo
• Format: Journal Article
• Language: English
• Published: England Company of Biologists 15.05.2012
• Subjects: Animals; Apoptosis - genetics; Apoptosis - physiology; beta Catenin - metabolism; Blotting, Western; catenin; Cell Movement - genetics; Cell Movement - physiology; Cell Proliferation; Cells, Cultured; Cleft Lip - genetics; Cleft Lip - metabolism; Cleft lip/palate; Cleft Palate - genetics; Cleft Palate - metabolism; Development; Fibroblast growth factor; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Gene expression; In Situ Hybridization; Jaw; Jaw - embryology; Jaw - metabolism; Lip; Lip - embryology; Lip - metabolism; Maxilla; Maxilla - embryology; Maxilla - metabolism; Mesenchyme; Mice; Mice, Knockout; Microscopy, Electron, Scanning; Mutation; Nose - embryology; Nose - metabolism; Organ Culture Techniques; Palate; Palate - embryology; Palate - metabolism; Real-Time Polymerase Chain Reaction; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.075796

Outgrowth and fusion of the lateral and medial nasal processes and of the maxillary process of the first branchial arch are integral to lip and primary palate development. Wnt9b mutations are associated with cleft lip and cleft palate in mice; however, the cause of these defects remains unknown. Here, we report that Wnt9b(-/-) mice show significantly retarded outgrowth of the nasal and maxillary processes due to reduced proliferation of mesenchymal cells, which subsequently results in a failure of physical contact between the facial processes that leads to cleft lip and cleft palate. These cellular defects in Wnt9b(-/-) mice are mainly caused by reduced FGF family gene expression and FGF signaling activity resulting from compromised canonical WNT/β-catenin signaling. Our study has identified a previously unknown regulatory link between WNT9B and FGF signaling during lip and upper jaw development.