title: ISLET1-Dependent β-Catenin/Hedgehog Signaling Is Required for Outgrowth of the Lower Jaw.
abstract: Mandibular patterning information initially resides in the epithelium during development. However, how transcriptional regulation of epithelium-derived signaling controls morphogenesis of the mandible remains elusive. UsingShhCreto target the mandibular epithelium, we ablated transcription factorIslet1, resulting in a distally truncated mandible via unbalanced cell apoptosis and decreased cell proliferation in the distal mesenchyme. Loss ofIslet1caused a lack of cartilage at the distal tip, leading the fusion of two growing mandibular elements surrounding the rostral process of Meckel's cartilage. Loss ofIslet1results in dysregulation of mesenchymal genes important for morphogenesis of the mandibular arch. We revealed thatIslet1is required for the activation of epithelial β-catenin signaling via repression of Wnt antagonists. Reactivation of β-catenin in the epithelium of theIslet1mutant rescued mandibular morphogenesis through sonic hedgehog (SHH) signaling to the mesenchyme. Furthermore, overexpression of a transgenic hedgehog ligand in the epithelium also partially restored outgrowth of the mandible. These data reveal functional roles for an ISLET1-dependent network integrating β-catenin/SHH signals in mesenchymal cell survival and outgrowth of the mandible during development.
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Feixue
authors.initials: F
authors.lastname: Li
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Fu
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Ying
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: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
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: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Yu
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Gan
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Zhejiang, China.
authors.forename: Mengsheng
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Molecular Cell Biology, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Tulane Medical Center, New Orleans, Louisiana, USA.
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 zunyi_zhang@idrbio.org.
authors.forename: Zunyi
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019521:Body Patterning; D002470:Cell Survival; D004475:Ectoderm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008334:Mandible / Q000196:embryology* / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C063843:insulin gene enhancer binding protein Isl-1
keywords: Islet1; SHH pathway; epithelium; mandibular growth; mesenchyme; β-catenin signaling