title: Wnt activation in nail epithelium couples nail growth to digit regeneration.
abstract: The tips of mammalian digits can regenerate after amputation, like those of amphibians. It is unknown why this capacity is limited to the area associated with the nail. Here we show that nail stem cells (NSCs) reside in the proximal nail matrix and that the mechanisms governing NSC differentiation are coupled directly with their ability to orchestrate digit regeneration. Early nail progenitors undergo Wnt-dependent differentiation into the nail. After amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to the regeneration of the digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate the nail or digit. Nevertheless, β-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NSC differentiation and digit regeneration, and suggest that NSCs may have the potential to contribute to the development of novel treatments for amputees.
authors.affiliation: The Ronald O. Perelman Department of Dermatology, New York University, School of Medicine, New York, New York 10016, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeo
authors.forename: Wei Chin
authors.initials: WC
authors.lastname: Chou
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Wendy
authors.initials: W
authors.lastname: Lee
authors.forename: Piul
authors.initials: P
authors.lastname: Rabbani
authors.forename: Cynthia
authors.initials: C
authors.lastname: Loomis
authors.forename: M Mark
authors.initials: MM
authors.lastname: Taketo
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ito
mesh_terms: D000671:Amputation, Surgical; D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D005121:Extremities / Q000254:growth & development / Q000294:innervation / Q000502:physiology*; D006724:Hoof and Claw / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin