Wnt-β-catenin signaling initiates taste papilla development

被引:124
|
作者
Liu, Fei
Thirumangalathu, Shoba
Gallant, Natalie M.
Yang, Steven H.
Stoick-Cooper, Cristi L.
Reddy, Seshamma T.
Andl, Thomas
Taketo, Makoto M.
Dlugosz, Andrzej A.
Moon, Randall T.
Barlow, Linda A. [1 ]
Millar, Sarah E.
机构
[1] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Cell & Dev Biol, Aurora, CO 80045 USA
[4] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA
[5] Univ Washington, Sch Med, Dept Pharmacol, Howard Hughes Med Inst, Seattle, WA 98195 USA
[6] Univ Washington, Sch Med, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA
[7] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan
关键词
D O I
10.1038/ng1932
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Fungiform taste papillae form a regular array on the dorsal tongue. Taste buds arise from papilla epithelium(1) and, unusually for epithelial derivatives, synapse with neurons, release neurotransmitters and generate receptor and action potentials(2,3). Despite the importance of taste as one of our five senses, genetic analyses of taste papilla and bud development are lacking. We demonstrate that Wnt-beta-catenin signaling is activated in developing fungiform placodes and taste bud cells. A dominant stabilizing mutation of epithelial beta-catenin causes massive overproduction of enlarged fungiform papillae and taste buds. Likewise, genetic deletion of epithelial beta-catenin or inhibition of Wnt-beta-catenin signaling by ectopic dickkopf1 (Dkk1)(4-6) blocks initiation of fungiform papilla morphogenesis. Ectopic papillae are innervated in the stabilizing beta-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation. Thus, Wnt-beta-catenin signaling is critical for fungiform papilla and taste bud development. Altered regulation of this pathway may underlie evolutionary changes in taste papilla patterning.
引用
收藏
页码:106 / 112
页数:7
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