Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis

Mutations in WNT effector genes perturb hair follicle morphogenesis, suggesting key roles for WNT proteins in this process. We show that expression of Wnts 10b and 10a is upregulated in placodes at the onset of follicle morphogenesis and in postnatal hair follicles beginning a new cycle of hair growth. The expression of additional Wnt genes is observed in follicles at later stages of differentiation. Among these, we find that Wnt5a is expressed in the developing dermal condensate of wild type but not Sonic hedgehog (Shh)-null embryos, indicating that Wnt5a is a target of SHH in hair follicle morphogenesis. These results identify candidates for several key follicular signals and suggest that WNT and SHH signaling pathways interact to regulate hair follicle morphogenesis.

[1]  C. Kozak,et al.  Isolation and genetic mapping of two novel members of the murine Wnt gene family, Wnt11 and Wnt12, and the mapping of Wnt5a and Wnt7a. , 1994, Genomics.

[2]  E. Fuchs,et al.  Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. , 1999, Development.

[3]  P. Beachy,et al.  Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function , 1996, Nature.

[4]  N. Dahmane,et al.  Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours , 1997, Nature.

[5]  R. Moon,et al.  Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development , 1996, The Journal of cell biology.

[6]  R. Moon,et al.  Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling , 1997, Nature.

[7]  J. Smith,et al.  Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. , 2000, Development.

[8]  W Gaffield,et al.  Essential role for Sonic hedgehog during hair follicle morphogenesis. , 1999, Developmental biology.

[9]  A. McMahon,et al.  Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development. , 1990, Genes & development.

[10]  J. Christiansen,et al.  Targeted disruption of the Wnt2 gene results in placentation defects. , 1996, Development.

[11]  G. Barsh,et al.  WNT signaling in the control of hair growth and structure. , 1999, Developmental biology.

[12]  G. Shackleford,et al.  Murine Wnt10a and Wnt10b: cloning and expression in developing limbs, face and skin of embryos and in adults. , 1996, Oncogene.

[13]  C. Chuong,et al.  Wnt-7 a in feather morphogenesis : involvement of anterior-posterior asymmetry and proximal-distal elongation demonstrated with an in vitro reconstitution model , 1999 .

[14]  T. Doetschman,et al.  The TGF-beta2 isoform is both a required and sufficient inducer of murine hair follicle morphogenesis. , 1999, Developmental biology.

[15]  D. Krause,et al.  Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Georgia Chenevix-Trench,et al.  Expression of β-Catenin, a Key Mediator of the WNT Signaling Pathway, in Basal Cell Carcinoma , 2000 .

[17]  Y. Barrandon,et al.  Conditional Disruption of Hedgehog Signaling Pathway Defines its Critical Role in Hair Development and Regeneration , 2000 .

[18]  S. Sokol,et al.  A role for Wnts in morpho-genesis and tissue polarity , 2000, Nature Cell Biology.

[19]  R. Moon,et al.  Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in aG-protein-dependent manner , 1999, Current Biology.

[20]  M. Klymkowsky,et al.  Cytoskeletal-membrane interactions and signal transduction , 1997 .

[21]  J. Sundberg,et al.  The role of the hairless (hr) gene in the regulation of hair follicle catagen transformation. , 1999, The American journal of pathology.

[22]  R. Nusse,et al.  Mechanisms of Wnt signaling in development. , 1998, Annual review of cell and developmental biology.

[23]  A. McMahon,et al.  The world according to hedgehog. , 1997, Trends in genetics : TIG.

[24]  R. Moon,et al.  Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos , 1995, Molecular and cellular biology.

[25]  M. Scott,et al.  Splitting Hairs Dissecting Roles of Signaling Systems in Epidermal Development , 1998, Cell.

[26]  R Paus,et al.  A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. , 1999, The Journal of investigative dermatology.

[27]  C. Hui,et al.  Basal cell carcinomas in mice overexpressing Gli2 in skin , 2000, Nature Genetics.

[28]  Michael Dean,et al.  Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome , 1996, Cell.

[29]  R. Nusse,et al.  Wnt signaling: a common theme in animal development. , 1997, Genes & development.

[30]  E. Fuchs,et al.  Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. , 1995, Genes & development.

[31]  Robert Geisler,et al.  Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation , 2000, Nature.

[32]  G. Barsh Of ancient tales and hairless tails , 1999, Nature Genetics.

[33]  S. Nishikawa,et al.  Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. , 2001, Development.

[34]  B. Powell,et al.  The Notch signalling pathway in hair growth , 1998, Mechanisms of Development.

[35]  C. Betsholtz,et al.  Roles for PDGF-A and sonic hedgehog in development of mesenchymal components of the hair follicle. , 1999, Development.

[36]  E. Fuchs,et al.  De Novo Hair Follicle Morphogenesis and Hair Tumors in Mice Expressing a Truncated β-Catenin in Skin , 1998, Cell.

[37]  Scott E. Fraser,et al.  Dishevelled controls cell polarity during Xenopus gastrulation , 2000, Nature.

[38]  R. Paus,et al.  Hair growth induction by substance P. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[39]  Steven J. M. Jones,et al.  A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. , 1999, Development.

[40]  Randall T Moon,et al.  Mechanism and function of signal transduction by the Wnt/β-catenin and Wnt/Ca2+ pathways , 1999, Oncogene.

[41]  R. Nusse,et al.  Expression of two members of the Wnt family during mouse development--restricted temporal and spatial patterns in the developing neural tube. , 1991, Genes & development.

[42]  C. Chuong,et al.  Early events during avian skin appendage regeneration: dependence on epithelial-mesenchymal interaction and order of molecular reappearance. , 1996, The Journal of investigative dermatology.

[43]  A. McMahon,et al.  Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. , 1993, Development.

[44]  E. Fuchs,et al.  A common human skin tumour is caused by activating mutations in beta-catenin. , 1999, Nature genetics.

[45]  E. Holmberg,et al.  Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the Gorlin syndrome: different in vivo mechanisms of PTCH inactivation. , 1996, Cancer research.

[46]  Harold E. Varmus,et al.  Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome , 1982, Cell.

[47]  R. Nusse,et al.  Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[48]  M M Newhouse,et al.  Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development. , 1996, Genes & development.

[49]  M. Scott,et al.  Basal cell carcinomas in mice overexpressing sonic hedgehog. , 1997, Science.

[50]  T. Sun,et al.  Label-retaining cells reside in the bulge area of pilosebaceous unit: Implications for follicular stem cells, hair cycle, and skin carcinogenesis , 1990, Cell.

[51]  M. Gessler,et al.  Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers. , 2000, Development.

[52]  R. Paus,et al.  Sonic hedgehog signaling is essential for hair development , 1998, Current Biology.

[53]  R. Crystal,et al.  Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog. , 1999, The Journal of clinical investigation.

[54]  A. Penzo-Méndez,et al.  The C‐terminal cytoplasmic Lys‐Thr‐X‐X‐X‐Trp motif in frizzled receptors mediates Wnt/β‐catenin signalling , 2000, The EMBO journal.

[55]  P. Leder,et al.  Wnt-10b directs hypermorphic development and transformation in mammary glands of male and female mice , 1997, Oncogene.

[56]  J. Nathans,et al.  A Member of the Frizzled Protein Family Mediating Axis Induction by Wnt-5A , 1997, Science.

[57]  J Galceran,et al.  Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development. , 1996, Genes & development.

[58]  M. Kumakiri,et al.  Ultrastructural Resemblance of Basal Cell Epithelioma to Primary Epithelial Germ , 1978, Journal of cutaneous pathology.

[59]  P. Adler The genetic control of tissue polarity in Drosophila , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[60]  Y. Barrandon,et al.  Regular articles: conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration. , 2000, The Journal of investigative dermatology.

[61]  B. Morgan,et al.  beta-catenin signaling can initiate feather bud development. , 1999, Development.

[62]  J. Riou,et al.  Role of frizzled 7 in the regulation of convergent extension movements during gastrulation in Xenopus laevis. , 2000, Development.

[63]  R. Myers,et al.  Human Homolog of patched, a Candidate Gene for the Basal Cell Nevus Syndrome , 1996, Science.

[64]  R. Nusse,et al.  Hedgehog signaling regulates transcription through cubitus interruptus, a sequence-specific DNA binding protein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[65]  C. H. Waddington,et al.  Mechanisms of Development , 1955, Nature.

[66]  C. Watson,et al.  Mouse Wnt8B is expressed in the developing forebrain and maps to Chromosome 19 , 1999, Mammalian Genome.

[67]  A. Majumdar,et al.  Zebrafish wnt4b expression in the floor plate is altered in sonic hedgehog and gli-2 mutants , 2000, Mechanisms of Development.

[68]  Nakazawa,et al.  Overexpression of the human homologue of Drosophila patched (PTCH) in skin tumours: specificity for basal cell carcinoma , 1999, The British journal of dermatology.

[69]  P. Chambon,et al.  A new mouse member of the Wnt gene family, mWnt-8, is expressed during early embryogenesis and is ectopically induced by retinoic acid , 1996, Mechanisms of Development.

[70]  R. Moon,et al.  Overlapping expression of Xwnt-3A and Xwnt-1 in neural tissue of Xenopus laevis embryos. , 1993, Developmental biology.

[71]  G Chenevix-Trench,et al.  Expression of beta-catenin, a key mediator of the WNT signaling pathway, in basal cell carcinoma. , 2000, Archives of dermatology.

[72]  T. Sun,et al.  Cells within the bulge region of mouse hair follicle transiently proliferate during early anagen: heterogeneity and functional differences of various hair cycles. , 1994, Differentiation; research in biological diversity.

[73]  Christoph Peters,et al.  Noggin is a mesenchymally derived stimulator of hair-follicle induction , 1999, Nature Cell Biology.

[74]  A. McMahon,et al.  Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips. , 1996, Development.

[75]  R. Moon,et al.  Wnt4 affects morphogenesis when misexpressed in the zebrafish embryo , 1995, Mechanisms of Development.

[76]  B. Hogan,et al.  Inhibition of Bmp signaling affects growth and differentiation in the anagen hair follicle , 2000, The EMBO journal.

[77]  C. Chuong,et al.  beta-catenin in epithelial morphogenesis: conversion of part of avian foot scales into feather buds with a mutated beta-catenin. , 2000, Developmental biology.

[78]  N. Perrimon,et al.  Differential Recruitment of Dishevelled Provides Signaling Specificity in the Planar Cell Polarity and Wingless Signaling Pathways in Drosophila, Planar Cell Polarity (pcp) Signaling Is Mediated by the Receptor Frizzled (fz) and Transduced by Dishevelled (dsh). Wingless (wg) Signaling Also Requires , 2022 .

[79]  D. Wilkinson,et al.  Murine Wnt-11 and Wnt-12 have temporally and spatially restricted expression patterns during embryonic development , 1995, Mechanisms of Development.

[80]  Andrew P. McMahon,et al.  The world according to bedgebog , 1997 .

[81]  I Fariñas,et al.  Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. , 1994, Genes & development.

[82]  A. Bowcock,et al.  Isolation of two novel WNT genes, WNT14 and WNT15, one of which (WNT15) is closely linked to WNT3 on human chromosome 17q21. , 1997, Genomics.

[83]  R. Oliver Dermal-epidermal interactions and hair growth. , 1991, The Journal of investigative dermatology.

[84]  H. Ohuchi,et al.  A chicken Wnt gene, Wnt-11, is involved in dermal development. , 1995, Biochemical and biophysical research communications.

[85]  C. Potten,et al.  Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of anagen. , 1999, The Journal of investigative dermatology.

[86]  Yann Barrandon,et al.  Morphogenesis and Renewal of Hair Follicles from Adult Multipotent Stem Cells , 2001, Cell.

[87]  S. Mann Prenatal formation of hair follicle types , , 1962 .

[88]  L. Sperling,et al.  Hair anatomy for the clinician. , 1991, Journal of the American Academy of Dermatology.

[89]  M. H. Hardy,et al.  The secret life of the hair follicle. , 1992, Trends in genetics : TIG.

[90]  E. Lane,et al.  Keratin expression in basal cell carcinomas , 1992, The British journal of dermatology.

[91]  P. Adler,et al.  A single frizzled protein has a dual function in tissue polarity. , 1994, Development.

[92]  Gina A. Taylor,et al.  Involvement of Follicular Stem Cells in Forming Not Only the Follicle but Also the Epidermis , 2000, Cell.

[93]  J. Shih,et al.  Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis. , 1993, Development.

[94]  R. Burgeson,et al.  Wnt signaling maintains the hair-inducing activity of the dermal papilla. , 2000, Genes & development.

[95]  W. Birchmeier,et al.  β-Catenin Controls Hair Follicle Morphogenesis and Stem Cell Differentiation in the Skin , 2001, Cell.

[96]  Stephen W. Wilson,et al.  Silberblick / Wnt 11 mediates convergent extension movements during zebra ® sh gastrulation , 2022 .

[97]  A. Brown,et al.  Transformation by Wnt family proteins correlates with regulation of beta-catenin. , 1997, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[98]  M. Holick,et al.  Control of hair growth with parathyroid hormone (7-34). , 1997, The Journal of investigative dermatology.

[99]  J. Downing,et al.  Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia. , 1999, Proceedings of the National Academy of Sciences of the United States of America.