CoChat
Sign Up
Cited by 66Hair Growth and DisordersSkin and Cellular Biology ResearchDevelopmental Biology and Gene Regulation

Sox2 modulates the function of two distinct cell lineages in mouse skin

Open access
Lesko, Marta H., Driskell, Ryan R., Kretzschmar, Kai, Goldie, Stephen J., Watt, Fiona M.·2013·Developmental Biology
DOI 10.1016/j.ydbio.2013.08.004PMC PMC3807655
Open this paper in CoChat — free account

Abstract

In postnatal skin the transcription factor Sox2 is expressed in the dermal papilla (DP) of guard/awl/auchene hair follicles and by mechanosensory Merkel cells in the touch domes of guard hairs. To investigate the consequences of Sox2 ablation in skin we deleted Sox2 in DP cells via Blimp1Cre and in Merkel cells via K14Cre. Loss of Sox2 from the DP did not inhibit hair follicle morphogenesis or establishment of the dermis and hypodermis. However, Sox2 expression in the DP was necessary for postnatal maintenance of awl/auchene hair follicles. Deletion of Sox2 via K14Cre resulted in a decreased number of Merkel cells but had no effect on other epithelial compartments or on the dermis. The reduced number of Merkel cells did not affect the number or patterning of guard hairs, nerve density or the interaction of nerve cells with the touch domes. We conclude that Sox2 is a marker of two distinct lineages in the skin and regulates the number of differentiated cells in the case of the Merkel cell lineage and hair follicle type in the case of the DP.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.ydbio.2013.08.004

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The bulb-like structures are reminiscent of nascent guard, awl, or auchene hair follicles.

    “We discovered that these structures were extensions of the KRT5+ epidermis and were associated with SOX2+ dermal papilla (DP)-like cells (Figure 1C, D), reminiscent of nascent guard, awl, or auchene HFs (Driskell et al., 2009; Lesko et al., 2013).”

    From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Lesko et al., 2013

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 46

  1. Arnold K. Sarkar A. Yram M.A. Polo J.M. Bronson R. Sengupta S. Seandel M. Geijsen N. Hochedlinger K. Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice Cell Stem Cell 9 2011 317 329 21982232 PMC3538360
  2. Avilion A.A. Nicolis S.K. Pevny L.H. Perez L. Vivian N. Lovell-Badge R. Multipotent cell lineages in early mouse development depend on Sox2 function Genes Dev. 17 2003 126 140 12514105 PMC195970
  3. Bardot E.S. Valdes V.J. Zhang J. Perdigoto C.N. Nicolis S. Hearn S.A. Silva J.M. Ezhkova E. Polycomb subunits Ezh1 and Ezh2 regulate the Merkel cell differentiation program in skin stem cells EMBO J. 32 2013 1990 2000 23673358 PMC3715854
  4. Biernaskie J. Paris M. Morozova O. Fagan B.M. Marra M. Pevny L. Miller F.D. SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells Cell Stem Cell 5 2009 610 623 19951689 PMC2828150
  5. Byrne C. Tainsky M. Fuchs E. Programming gene expression in developing epidermis Development 120 1994 2369 2383 7525178
  6. Chi W. Wu E. Morgan B.A. Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline Development 140 2013 1676 1678 23487317 PMC3621486
  7. Clavel C. Grisanti L. Zemla R. Rezza A. Barros R. Sennett R. Mazloom A.R. Chung C.Y. Cai X. Cai C.L. Pevny L. Nicolis S. Ma’ayan A. Rendl M. Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP signaling in differentiating hair shaft progenitors Dev. Cell 23 2012 981 994 23153495 PMC3500526
  8. Doucet Y.S. Woo S.H. Ruiz M.E. Owens D.M.. The touch dome defines an epidermal niche specialized for mechanosensory signaling Cell Rep. 3 2013 1759 1765 23727240 PMC3700648
  9. Driskell R.R. Clavel C. Rendl M. Watt F.M. Hair follicle dermal papilla cells at a glance J. Cell Sci. 124 2011 1179 1182 21444748 PMC3115771
  10. Driskell I. Oda H. Blanco S. Nascimento E. Humphreys P. Frye M. The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin EMBO J. 31 2012 616 629 22117221 PMC3273381
  11. Driskell R.R. Juneja V.R. Connelly J.T. Kretzschmar K. Tan D.W.-M. Watt F.M. Clonal growth of dermal papilla cells in hydrogels reveals intrinsic differences between Sox2-positive and -negative cells in vitro and in vivo J. Invest. Dermatol. 132 2012 1084 1093 22189784 PMC3306894
  12. Eispert A.-C. Fuchs F. Brandner J.M. Houdek P. Wladykowski E. Moll I. Evidence for distinct populations of human Merkel cells Histochem. Cell. Biol. 132 2009 83 93 19319559
  13. Enshell-Seijffers D. Lindon C. Kashiwagi M. Morgan B.A. Beta-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair Dev. Cell 18 2010 633 642 20412777 PMC2893731
  14. Enshell-Seijffers D. Lindon C. Morgan B.A. The serine protease Corin is a novel modifier of the Agouti pathway Development 135 2008 217 225 18057101 PMC2186067
  15. Favaro R. Valotta M. Ferri A.L. Latorre E. Mariani J. Giachino C. Lancini C. Tosetti V. Ottolenghi S. Taylor V. Nicolis S.K. Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh Nat. Neurosci. 12 2009 1248 1256 19734891
  16. Fernandes K.J. McKenzie I.A. Mill P. Smith K.M. Akhavan M. Barnabe-Heider F. Biernaskie J. Junek A. Kobayashi N.R. Toma J.G. Kaplan D.R. Labosky P.A. Rafuse V. Hui C.C. Miller F.D. A dermal niche for multipotent adult skin-derived precursor cells Nat. Cell Biol. 6 2004 1082 1093 15517002
  17. Grisanti L. Clavel C. Cai X. Rezza A. Tsai S.Y. Sennett R. Mumau M. Cai C.L. Rendl M. Tbx18 targets dermal condensates for labeling, isolation, and gene ablation during embryonic hair follicle formation J. Invest. Dermatol. 133 2013 344 353 22992803 PMC3530628
  18. Haeberle H. Fujiwara M. Chuang J. Medina M.M. Panditrao M.V. Bechstedt S. Howard J. Lumpkin E.A. Molecular profiling reveals synaptic release machinery in Merkel cells Proc. Natl. Acad. Sci. USA 101 2004 14503 14508 15448211 PMC521975
  19. Haeberle H. Bryan L.A. Vadakkan T.J. Dickinson M.E. Lumpkin E.A. Swelling-activated Ca2+ channels trigger Ca2+ signals in Merkel cells PLoS One 3 2008 e1750 18454189 PMC2365925
  20. Hamburg E.J. Atit R.P. Sustained β-catenin activity in dermal fibroblasts is sufficient for skin fibrosis J. Invest. Dermatol. 132 2012 2469 2472 22622416 PMC3430808
  21. Horsley Carroll V.O’ Tooze D. Ohinata R. Saitou Y. Obukhanych M. Nussenzweig T. Tarakhovsky M. Fuchs A. E. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland Cell 126 2006 597 609 16901790 PMC2424190
  22. Ito Y. Hamazaki T.S. Ohnuma K. Tamaki K. Asashima M. Okochi H. Isolation of murine hair-inducing cells using the cell surface marker prominin-1/CD133 J. Invest. Dermatol. 127 2007 1052 1060 17185982
  23. James K. Hosking B. Gardner J. Muscat G.E. Koopman P. Sox18 mutations in the ragged mouse alleles ragged-like and opossum Genesis 36 2003 1 6 12748961
  24. Jensen K.B. Driskell R.R. Watt F.M. Assaying proliferation and differentiation capacity of stem cells using disaggregated adult mouse epidermis Nat. Protoc. 5 2010 898 911 20431535
  25. Kawamoto S. Niwa H. Tashiro F. Sano S. Kondoh G. Takeda J. Tabayashi K. Miyazaki J. A novel reporter mouse strain that expresses enhanced green fluorescent protein upon Cre-mediated recombination FEBS Lett. 470 2000 263 268 10745079
  26. Laga A.C. Lai C.-Y. Zhan Q. Huang S.J. Velazquez E.F. Yang Q. Hsu M.-Y. Murphy G.F. Expression of the embryonic stem cell transcription factor Sox2 in human skin: relevance to melanocyte and merkel cell biology Am. J. Pathol. 176 2010 903 913 20042675 PMC2808095
  27. Lucarz A. Brand G. Current considerations about Merkel cells Eur. J. Cell Biol. 86 2007 243 251 17337089
  28. Lumpkin E.A. Caterina M.J. Mechanisms of sensory transduction in the skin Nature 445 2007 858 865 17314972
  29. Lumpkin E.A. Marshall K.L. Nelson A.M. The cell biology of touch J. Cell Biol. 191 2010 237 248 20956378 PMC2958478
  30. Maricich S.M. Wellnitz S.A. Nelson A.M. Lesniak D.R. Gerling G.J. Lumpkin E.A. Zoghbi H.Y. Merkel cells are essential for light-touch responses Science 324 2009 1580 1582 19541997 PMC2743005
  31. Millar S.E. Mechanisms Regulating Hair Follicle Dev J. Invest. Dematol. 118 2002 216 225 11841536
  32. Morrison K.M. Miesegaes G.R. Lumpkin E.A. Maricich S.M. Mammalian Merkel cells are descended from the epidermal lineage Dev. Biol. 336 2009 76 83 19782676 PMC2783667
  33. Narisawa Y. Hashimoto K. Immunohistochemical demonstration of nerve–Merkel cell complex in fetal human skin J. Dermatol. Sci. 2 1991 361 370 1720659
  34. Ohinata Y. Payer B. O’Carroll D. Ancelin K. Ono Y. Sano M. Barton S.C. Obukhanych T. Nussenzweig M. Tarakhovsky A. Saitou M. Surani M.A. Blimp1 is a critical determinant of the germ cell lineage in mice Nature 436 2005 207 213 15937476
  35. Pevny L.H. Nicolis S.K. Sox2 roles in neural stem cells Int. J. Biochem. Cell Biol. 42 2010 421 424 19733254
  36. Piskorowski R. Haeberle H. Panditrao M.V. Lumpkin E.A. Voltage-activated ion channels and Ca(2+)-induced Ca (2+) release shape Ca (2+) signaling in Merkel cells Pflugers Arch. 457 2008 197 209 18415122 PMC2574749
  37. Rendl M. Lewis L. Fuchs E. Molecular dissection of mesenchymal-epithelial interactions in the hair follicle PLoS Biol. 3 2005 e331 16162033 PMC1216328
  38. Robertson E.J. Charatsi I. Joyner C.J. Koonce C.H. Morgan M. Islam A. Paterson C. Lejsek E. Arnold S.J. Kallies A. Nutt S.L. Bikoff E.K. Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice Development 134 2007 4335 4345 18039967 PMC7116377
  39. Scott S.A. Cooper E. Diamond J. Merkel cells as targets of the mechanosensory nerves in salamander skin Proc. R. Soc. London, B, Biol. Sci. 211 1981 455 470 6112757
  40. Tachibana T. Yamamoto H. Takahashi N. Kamegai T. Shibanai S. Iseki H. Nawa T. Polymorphism of Merkel cells in the rodent palatine mucosa: immunohistochemical and ultrastructural studies Arch. Histol. Cytol. 60 1997 379 389 9412741
  41. Takahashi K. Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors Cell 126 2006 663 676 16904174
  42. Toma J.G. Akhavan M. Fernandes K.J. Barnabe-Heider F. Sadikot A. Kaplan D.R. Miller F.D. Isolation of multipotent adult stem cells from the dermis of mammalian skin Nat. Cell Biol. 3 2001 778 784 11533656
  43. Van Keymeulen A. Mascre G. Youseff K.K. Harel I. Michaux C. De Geest N. Szpalski C. Achouri Y. Bloch W. Hassan B.A. Blanpain C. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homoeostasis J. Cell Biol. 187 2009 91 100 19786578 PMC2762088
  44. Woo S.-H. Stumpfova M. Jensen U.B. Lumpkin E.A. Owens D.M. Identification of epidermal progenitors for the Merkel cell lineage Development 137 2010 3965 3971 21041368 PMC2976280
  45. Woo W.M. Zhen H.H. Oro A.E. Shh maintains dermal papilla identity and hair morphogenesis via a Noggin-Shh regulatory loop Genes Dev. 26 2012 1235 1246 22661232 PMC3371411
  46. Zhou P. Byrne C. Jacobs J. Fuchs E. Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate Genes Dev. 9 1995 700 713 7537238

Cited by

Sorted by citations

Authors
Lesko, M. H., Driskell, R. R., Kretzschmar, K., Goldie, S. J., & Watt, F. M.
Affiliations
  • King's College London (GB)
  • Cancer Research UK (GB)
Corresponding author
Watt, Fiona M.
ORCID
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2013-10
Volume
382
Issue
1
Pages
15-26
ISSN
0012-1606 (ISSN-L)
DOI
10.1016/j.ydbio.2013.08.004
PMC
PMC3807655
OpenAlex
W2002700409
Cited by
66
References
5
Citations by year
2026: 4 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 12 · 2016: 2 · 2015: 5 · 2014: 11 · 2013: 1
FWCI
7.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, other-oa)
Funders
the MRC, Wellcome Trust, Cancer Research UK and the EU FP7
Topics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
SOX2, dermal papilla, Merkel cells, hair follicle morphogenesis, guard hair, touch domes, mechanosensory cells
MeSH terms
Positive Regulatory Domain I-Binding Factor 1, Epidermal Cells, Animals, Animals, Newborn, Cell Count, Epidermis, Homeostasis, Morphogenesis, Skin, Synapses, Transcription Factors, Vibrissae, Gene Deletion, Hair Follicle, Merkel Cells, Cell Lineage, Integrases, Body Patterning, Dermis, Mice, Keratin-14, SOXB1 Transcription Factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review