Lgr6 marks nail stem cells and is required for digit tip regeneration

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 43, 2015, Pages 13249-13254

  Lehoczky, Jessica A ^a   Tabin, Clifford J ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Epimorphic regeneration; Lgr5; Nail fold; Nail matrix; Wnt signaling

Indexed keywords

BETA CATENIN; G PROTEIN COUPLED RECEPTOR; LEUCINE RICH REPEAT CONTAINING G PROTEIN COUPLED RECEPTOR 5; LEUCINE RICH REPEAT CONTAINING G PROTEIN COUPLED RECEPTOR 6; UNCLASSIFIED DRUG; WNT PROTEIN; 5-BROMO-4-CHLORO-3-INDOLYL BETA-GALACTOSIDE; ALIZARIN; ANTHRAQUINONE DERIVATIVE; ENHANCED GREEN FLUORESCENT PROTEIN; GALACTOSIDE; GREEN FLUORESCENT PROTEIN; INDOLE DERIVATIVE; LGR6 PROTEIN, MOUSE; PRIMER DNA;

ANIMAL EXPERIMENT; ARTICLE; BLASTEMA; BONE REGENERATION; CANONICAL ANALYSIS; CELL FUNCTION; CELL POPULATION; DIGIT TIP REGENERATION; EPITHELIUM CELL; FEMALE; IMMUNOHISTOCHEMISTRY; MOUSE; NAIL STEM CELL; NONHUMAN; NULL ALLELE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN HOMEOSTASIS; SIGNAL TRANSDUCTION; STEM CELL; SWEAT GLAND; TISSUE REGENERATION; WNT SIGNALING PATHWAY; ANIMAL; CYTOLOGY; GENE INACTIVATION; GENETICS; HINDLIMB; HISTOLOGY; HOOF AND CLAW; METABOLISM; PHYSIOLOGY; REGENERATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TOE; TRANSGENIC MOUSE;

ANIMALS; ANTHRAQUINONES; DNA PRIMERS; EPITHELIAL CELLS; GALACTOSIDES; GENE KNOCKOUT TECHNIQUES; GREEN FLUORESCENT PROTEINS; HINDLIMB; HISTOLOGICAL TECHNIQUES; HOOF AND CLAW; IMMUNOHISTOCHEMISTRY; INDOLES; MICE; MICE, TRANSGENIC; RECEPTORS, G-PROTEIN-COUPLED; REGENERATION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TOES;

EID: 84945580377     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1518874112     Document Type: Article

References (41)

1. Kierdorf U, Li C, Price JS (2009) Improbable appendages: Deer antler renewal as a unique case of mammalian regeneration. Semin Cell Dev Biol 20(5):535-542.
2. Borgens RB (1982) Mice regrow the tips of their foretoes. Science 217(4561):747-750.
3. Singer M, Weckesser EC, Géraudie J, Maier CE, Singer J (1987) Open finger tip healing and replacement after distal amputation in rhesus monkey with comparison to limb regeneration in lower vertebrates. Anat Embryol (Berl) 177(1):29-36.
4. Illingworth CM (1974) Trapped fingers and amputated finger tips in children. J Pediatr Surg 9(6):853-858.
5. Douglas BS (1972) Conservative management of guillotine amputation of the finger in children. Aust Paediatr J 8(2):86-89.
6. Lehoczky JA, Robert B, Tabin CJ (2011) Mouse digit tip regeneration is mediated by fate-restricted progenitor cells. Proc Natl Acad Sci USA 108(51):20609-20614.
7. Rinkevich Y, Lindau P, Ueno H, Longaker MT, Weissman IL (2011) Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip. Nature 476(7361): 409-413.
8. Neufeld DA, Zhao W (1995) Bone regrowth after digit tip amputation in mice is equivalent in adults and neonates. Wound Repair Regen 3(4):461-466.
9. Mohammad KS, Day FA, Neufeld DA (1999) Bone growth is induced by nail transplantation in amputated proximal phalanges. Calcif Tissue Int 65(5):408-410.
10. Takeo M, et al. (2013) Wnt activation in nail epithelium couples nail growth to digit regeneration. Nature 499(7457):228-232.
11. Zaias N, Alvarez J (1968) The formation of the primate nail plate: An autoradiographic study in squirrel monkey. J Invest Dermatol 51(2):120-136.
12. Nakamura M, Ishikawa O (2008) The localization of label-retaining cells in mouse nails. J Invest Dermatol 128(3):728-730.
13. de Lau W, Peng WC, Gros P, Clevers H (2014) The R-spondin/Lgr5/Rnf43 module: Regulator of Wnt signal strength. Genes Dev 28(4):305-316.
14. Yi J, et al. (2013) Analysis of LGR4 receptor distribution in human and mouse tissues. PLoS One 8(10):e78144.
15. Van Schoore G, Mendive F, Pochet R, Vassart G (2005) Expression pattern of the orphan receptor LGR4/GPR48 gene in the mouse. Histochem Cell Biol 124(1):35-50.
16. Barker N, Tan S, Clevers H (2013) Lgr proteins in epithelial stem cell biology. Development 140(12):2484-2494.
17. Barker N, et al. (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449(7165):1003-1007.
18. Jaks V, et al. (2008) Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet 40(11):1291-1299.
19. Snippert HJ, et al. (2010) Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 327(5971):1385-1389.
20. Stoick-Cooper CL, et al. (2007) Distinct Wnt signaling pathways have opposing roles in appendage regeneration. Development 134(3):479-489.
21. Lin G, Slack JM (2008) Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration. Dev Biol 316(2):323-335.
22. Kawakami Y, et al. (2001) WNT signals control FGF-dependent limb initiation and AER induction in the chick embryo. Cell 104(6):891-900.
23. Clevers H, Loh KM, Nusse R (2014) Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 346(6205): 1248012.
24. Baron R, Kneissel M (2013) WNT signaling in bone homeostasis and disease: From human mutations to treatments. Nat Med 19(2):179-192.
25. Han M, Yang X, Lee J, Allan CH, Muneoka K (2008) Development and regeneration of the neonatal digit tip in mice. Dev Biol 315(1):125-135.
26. Sellheyer K, Nelson P (2012) The ventral proximal nail fold: Stem cell niche of the nail and equivalent to the follicular bulge-a study on developing human skin. J Cutan Pathol 39(9):835-843.
27. Yee KK, et al. (2013) Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue. Stem Cells 31(5):992-1000.
28. Plaks V, et al. (2013) Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis. Cell Reports 3(1):70-78.
29. Ng A, et al. (2014) Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat Cell Biol 16(8):745-757.
30. Barker N, et al. (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6(1):25-36.
31. de Lau W, et al. (2011) Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476(7360):293-297.
32. Fuchs E, Horsley V (2008) More than one way to skin. Genes Dev 22(8):976-985.
33. Gong X, et al. (2012) LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor. PLoS One 7(5):e37137.
34. Carmon KS, Gong X, Lin Q, Thomas A, Liu Q (2011) R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc Natl Acad Sci USA 108(28):11452-11457.
35. Leung Y, et al. (2014) Bifunctional ectodermal stem cells around the nail display dual fate homeostasis and adaptive wounding response toward nail regeneration. Proc Natl Acad Sci USA 111(42):15114-15119.
36. Lee DY, et al. (2012) The presence and localization of onychodermis (specialized nail mesenchyme) containing onychofibroblasts in the nail unit: A morphological and immunohistochemical study. Histopathology 61(1):123-130.
37. Sellheyer K, Nelson P (2013) The concept of the onychodermis (specialized nail mes-enchyme): An embryological assessment and a comparative analysis with the hair follicle. J Cutan Pathol 40(5):463-471.
38. Sorrell JM, Caplan AI (2004) Fibroblast heterogeneity: More than skin deep. J Cell Sci 117(Pt 5):667-675.
39. Rinkevich Y, et al. (2015) Skin fibrosis: Identification and isolation of a dermal lineage with intrinsic fibrogenic potential. Science 348(6232):420-431.
40. Tian H, et al. (2011) A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478(7368):255-259.
41. Murtaugh LC, Chyung JH, Lassar AB (1999) Sonic hedgehog promotes somitic chon-drogenesis by altering the cellular response to BMP signaling. Genes Dev 13(2): 225-237.