title: Ectodermal Wnt controls nasal pit morphogenesis through modulation of the BMP/FGF/JNK signaling axis.
abstract: BACKGROUND
  Mutations of WNT3, WNT5A, WNT9B, and WNT11 genes are associated with orofacial birth defects, including nonsyndromic cleft lip with cleft palate in humans. However, the source of Wnt ligands and their signaling effects on the orofacial morphogenetic process remain elusive.
  
  
  RESULTS
  Using Foxg1-Cre to impair Wnt secretion through the inactivation of Gpr177/mWls, we investigate the relevant regulation of Wnt production and signaling in nasal-facial development. Ectodermal ablation of Gpr177 leads to severe facial deformities resulting from dramatically reduced cell proliferation and increased cell death due to a combined loss of WNT, FGF and BMP signaling in the developing facial prominence. In the invaginating nasal pit, the Gpr177 disruption also causes a detrimental effect on migration of the olfactory epithelial cells into the mesenchymal region. The blockage of Wnt secretion apparently impairs the olfactory epithelial cells through modulation of JNK signaling.
  
  
  CONCLUSIONS
  Our study thus suggests the head ectoderm, including the facial ectoderm and the neuroectoderm, as the source of canonical as well as noncanonical Wnt ligands during early development of the nasal-facial prominence. Both β-catenin-dependent and -independent signaling pathways are required for proper development of these morphogenetic processes.
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Zhu
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Wanxin
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Genetics, Center for Oral Biology, James P Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York.
authors.forename: Wei
authors.initials: W
authors.lastname: Hsu
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.|Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky.
authors.forename: Mengsheng
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Ophthalmology, Tulane University Medical center, New Orleans, Louisiana.
authors.forename: Ze
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Zunyi
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004475:Ectoderm / Q000166:cytology / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology; D009296:Nasal Cavity / Q000196:embryology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors; D048670:MAP Kinase Kinase 4
keywords: Gpr177; JNK; Wntless; canonical Wnt; nasal pit; noncanonical Wnt