title: Gpr177-mediated Wnt Signaling is Required for Fungiform Placode Initiation.
abstract: Fungiform papillae are formed as patterned rows on the surface of the anterior tongue at early organogenesis and contain one taste bud in each papilla to form one of the important sensory organs. Despite the essential role of Wnt/β-catenin signaling in controlling the development of fungiform taste papillae, the universal function of Wnt ligands in the initiation of the fungiform placode has not been completely elucidated. Here, by Shh (Cre) -mediated oral epithelial deletion of Wntless (Gpr177), a regulator essential for intracellular Wnt trafficking, we demonstrate that an overall function of Wnts is required for initiation of the fungiform placode. Multiple Wnts are expressed in the tongue epithelium at E11.5 before initiation of the fungiform placodes. Epithelial Gpr177 loss-of-function, associated with reduction of canonical Wnt signaling in lingual epithelium as exhibited by a loss of TopGal activity and Axin2 expression, results in the failure of fungiform placode initiation, as assessed by diminished expression of several taste placode molecular markers. Moreover, LiCl treatment of Gpr177 epithelial-deficient tongue explants at E11.5, but not at E12.5, restores tongue placode formation, demonstrating that Wnt ligands in the tongue surface prior to but not after fungiform placode initiation are responsible for fungiform papilla initiation. Epithelium-specific expression of an active β-catenin in the Gpr177-deficient tongue leads to fungiform papillae generation, suggesting that an intra-epithelial response to Wnts is required for placode initiation. Together, these results suggest that Gpr177 controls epithelial initiation of the fungiform placode through signaling via epithelial Wnt ligands.
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, 16 XueLin Street, Xiasha, Hangzhou 310036, Zhejiang, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, 16 XueLin Street, Xiasha, Hangzhou 310036, Zhejiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, 16 XueLin Street, Xiasha, Hangzhou 310036, Zhejiang, China.
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, 16 XueLin Street, Xiasha, Hangzhou 310036, Zhejiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, 16 XueLin Street, Xiasha, Hangzhou 310036, Zhejiang, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, 16 XueLin Street, Xiasha, Hangzhou 310036, Zhejiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, 16 XueLin Street, Xiasha, Hangzhou 310036, Zhejiang, China.
authors.forename: M
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, 16 XueLin Street, Xiasha, Hangzhou 310036, Zhejiang, China zunyi_zhang@idrbio.org.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D004848:Epithelium / Q000196:embryology; D053823:Hedgehog Proteins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000502:physiology*; D018021:Lithium Chloride / Q000494:pharmacology; D008648:Mesoderm / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology*; D013650:Taste Buds / Q000187:drug effects / Q000196:embryology*; D046509:Tissue Culture Techniques; D014059:Tongue / Q000196:embryology; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; C545200:Gpr177 protein, mouse; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C465570:Shh protein, mouse; D051153:Wnt Proteins; D018021:Lithium Chloride
keywords: ShhCre; Wntless; canonical Wnt; fungiform papilla; taste placode; tongue