Signaling Involved in Hair Follicle Morphogenesis and Development

Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an essential role during hair follicle induction, Shh is involved in morphogenesis and late stage differentiation, Notch signaling determines stem cell fate while BMP is involved in cellular differentiation. The Wnt pathway is considered to be the master regulator during hair follicle morphogenesis. Wnt signaling proceeds through EDA/EDAR/NF-κB signaling. NF-κB regulates the Wnt pathway and acts as a signal mediator by upregulating the expression of Shh ligand. Signal crosstalk between epithelial and mesenchymal cells takes place mainly through primary cilia. Primary cilia formation is initiated with epithelial laminin-511 interaction with dermal β-1 integrin, which also upregulates expression of downstream effectors of Shh pathway in dermal lineage. PDGF signal transduction essential for crosstalk is mediated through epithelial PDGF-A and PDGFRα expressed on the primary cilia. Dermal Shh and PDGF signaling up-regulates dermal noggin expression; noggin is a potent inhibitor of BMP signaling which helps in counteracting BMP mediated β-catenin inhibition. This interplay of signaling between the epithelial and dermal lineage helps in epithelial Shh signal amplification. The dermal Wnt pathway helps in upregulation of epithelial Notch expression. Dysregulation of these pathways leads to certain abnormalities and in some cases even tumor outgrowth.

[1]  R. Paus,et al.  Noggin is required for induction of the hair follicle growth phase in postnatal skin , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  P. Jackson,et al.  Dual degradation signals control Gli protein stability and tumor formation. , 2006, Genes & development.

[3]  R. Smart,et al.  An estrogen receptor pathway regulates the telogen-anagen hair follicle transition and influences epidermal cell proliferation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Pekka Nieminen,et al.  Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. , 2002, Development.

[5]  G. Feng,et al.  Wls Is Expressed in the Epidermis and Regulates Embryonic Hair Follicle Induction in Mice , 2012, PloS one.

[6]  G. Dotto,et al.  Control of murine hair follicle regression (catagen) by TGF‐β1 in vivo , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  W. Pear,et al.  Impaired notch signaling promotes de novo squamous cell carcinoma formation. , 2006, Cancer research.

[8]  R. Paus,et al.  Molecular principles of hair follicle induction and morphogenesis , 2005, BioEssays : news and reviews in molecular, cellular and developmental biology.

[9]  K. Miyazono,et al.  Two major Smad pathways in TGF‐β superfamily signalling , 2002, Genes to cells : devoted to molecular & cellular mechanisms.

[10]  Elaine Fuchs,et al.  A Signaling Pathway Involving TGF-β2 and Snail in Hair Follicle Morphogenesis , 2004, PLoS biology.

[11]  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.

[12]  E. Fuchs,et al.  BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties. , 2008, Genes & development.

[13]  R. Sennett,et al.  Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling. , 2012, Seminars in cell & developmental biology.

[14]  Penny Rashbass,et al.  Foxn1 is required for tissue assembly and desmosomal cadherin expression in the hair shaft , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[15]  A. Brivanlou,et al.  APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex , 2010, Nature.

[16]  Y. Barrandon,et al.  The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle. , 2001, Genes & development.

[17]  D. Sredni,et al.  Opposite effects of FGF and BMP-4 on embryonic blood formation: roles of PV.1 and GATA-2. , 1999, Developmental biology.

[18]  Q. Gu,et al.  Activating Smoothened mutations in sporadic basal-cell carcinoma , 1998, Nature.

[19]  J. Reiter,et al.  Wounding mobilizes hair follicle stem cells to form tumors , 2011, Proceedings of the National Academy of Sciences.

[20]  Hans Clevers,et al.  The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. , 2002, Cell.

[21]  Duane D. Miller,et al.  MicroRNAs Are Mediators of Androgen Action in Prostate and Muscle , 2010, PloS one.

[22]  Maria I Morasso,et al.  Dlx3 is a crucial regulator of hair follicle differentiation and cycling , 2008, Development.

[23]  Yann Barrandon,et al.  Long-term renewal of hair follicles from clonogenic multipotent stem cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  N. Vlahov,et al.  Micro‐RNA‐31 controls hair cycle‐associated changes in gene expression programs of the skin and hair follicle , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  R. Patient,et al.  GATA‐6 maintains BMP‐4 and Nkx2 expression during cardiomyocyte precursor maturation , 2003, The EMBO journal.

[26]  R. Paus,et al.  What controls hair follicle cycling? , 1999, Experimental dermatology.

[27]  Angela M. Christiano,et al.  KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin , 2009, Development.

[28]  C. Hill,et al.  New insights into TGF-beta-Smad signalling. , 2004, Trends in biochemical sciences.

[29]  J. Massagué,et al.  Smad transcription factors. , 2005, Genes & development.

[30]  Avi Ma'ayan,et al.  Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP signaling in differentiating hair shaft progenitors. , 2012, Developmental cell.

[31]  H. Pasolli,et al.  A two-step mechanism for stem cell activation during hair regeneration. , 2009, Cell stem cell.

[32]  K. Higgins,et al.  Hair cycle regulation of Hedgehog signal reception. , 2003, Developmental biology.

[33]  K. Miyazono,et al.  Divergence and convergence of TGF‐β/BMP signaling , 2001, Journal of cellular physiology.

[34]  E. Fuchs,et al.  Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA , 2003, The Journal of cell biology.

[35]  E. Fuchs,et al.  Links between signal transduction, transcription and adhesion in epithelial bud development , 2003, Nature.

[36]  P. Warne,et al.  Role of Phosphoinositide 3-OH Kinase in Cell Transformation and Control of the Actin Cytoskeleton by Ras , 1997, Cell.

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

[38]  Piul S. Rabbani,et al.  Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration , 2011, Cell.

[39]  Benjamin D. Yu,et al.  Negative regulation of Shh levels by Kras and Fgfr2 during hair follicle development. , 2013, Developmental biology.

[40]  Yadong Yang,et al.  Versican gene: regulation by the β-catenin signaling pathway plays a significant role in dermal papilla cell aggregative growth. , 2012, Journal of dermatological science.

[41]  E. Fuchs,et al.  Architectural Niche Organization by LHX2 is Linked to Hair Follicle Stem Cell Function , 2014 .

[42]  B. Morgan,et al.  beta-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. , 2010, Developmental cell.

[43]  H. Clevers,et al.  Lgr6 Marks Stem Cells in the Hair Follicle That Generate All Cell Lineages of the Skin , 2010, Science.

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

[45]  N. Sato,et al.  β‐Catenin gene mutation in human hair follicle‐related tumors , 2001, Pathology international.

[46]  J. Nicolas,et al.  Hair follicle renewal: organization of stem cells in the matrix and the role of stereotyped lineages and behaviors , 2005, Development.

[47]  M. Capecchi,et al.  Hoxc13 mutant mice lack external hair. , 1998, Genes & development.

[48]  A. Dlugosz.  The Hedgehog and the hair follicle: a growing relationship. , 1999, The Journal of clinical investigation.

[49]  François Vaillant,et al.  Generation of a functional mammary gland from a single stem cell , 2006, Nature.

[50]  Yaping Liu,et al.  Capturing and profiling adult hair follicle stem cells , 2004, Nature Biotechnology.

[51]  F. Watt,et al.  Epidermal Notch signalling: differentiation, cancer and adhesion , 2008, Current opinion in cell biology.

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

[53]  T. Ito,et al.  Overexpression of Hoxc13 in differentiating keratinocytes results in downregulation of a novel hair keratin gene cluster and alopecia. , 2001, Development.

[54]  S. Millar,et al.  WNT signals are required for the initiation of hair follicle development. , 2002, Developmental cell.

[55]  S. Inui,et al.  Roles of MED1 in quiescence of hair follicle stem cells and maintenance of normal hair cycling. , 2013, The Journal of investigative dermatology.

[56]  E. Fuchs,et al.  Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. , 2001, Genes & development.

[57]  T. Tumbar,et al.  Runx1 modulates adult hair follicle stem cell emergence and maintenance from distinct embryonic skin compartments , 2011, The Journal of cell biology.

[58]  C. Callahan,et al.  Monstrous attempts at adnexogenesis: regulating hair follicle progenitors through Sonic hedgehog signaling. , 2001, Current opinion in genetics & development.

[59]  David Shalloway,et al.  Runx1 and p21 synergistically limit the extent of hair follicle stem cell quiescence in vivo , 2013, Proceedings of the National Academy of Sciences.

[60]  Xi C. He,et al.  Bone Morphogenetic Protein Signaling Inhibits Hair Follicle Anagen Induction by Restricting Epithelial Stem/Progenitor Cell Activation and Expansion , 2006, Stem cells.

[61]  M. Koster,et al.  Roles of TGFbeta signaling in epidermal/appendage development. , 2003, Cytokine & growth factor reviews.

[62]  S. Bray.  Notch signalling: a simple pathway becomes complex , 2006, Nature Reviews Molecular Cell Biology.

[63]  C. Kwak,et al.  Effect of dominant negative transforming growth factor-beta receptor type II on cytotoxic activity of RAW 264.7, a murine macrophage cell line. , 2007, Cancer research.

[64]  J. Toribio,et al.  Hereditary hypotrichosis simplex of the scalp , 1974, The British journal of dermatology.

[65]  Andrew P McMahon,et al.  Developmental roles and clinical significance of hedgehog signaling. , 2003, Current topics in developmental biology.

[66]  Boris Jerchow,et al.  Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction. , 2009, Developmental cell.

[67]  Pascal Schneider,et al.  Generation of the primary hair follicle pattern. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Y. Mishina.  Function of bone morphogenetic protein signaling during mouse development. , 2003, Frontiers in bioscience : a journal and virtual library.

[69]  A. Sharov,et al.  MicroRNA-21 is an important downstream component of BMP signalling in epidermal keratinocytes , 2011, Development.

[70]  V. Botchkarev,et al.  Molecular control of epithelial-mesenchymal interactions during hair follicle cycling. , 2003, The journal of investigative dermatology. Symposium proceedings.

[71]  S. Ivy,et al.  Molecular Conversations and the Development of the Hair Follicle and Basal Cell Carcinoma , 2010, Cancer Prevention Research.

[72]  C. Chuong,et al.  `Cyclic alopecia' in Msx2 mutants: defects in hair cycling and hair shaft differentiation , 2003, Development.

[73]  R. Atit,et al.  Dermal β-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation , 2012, Development.

[74]  J. Massagué,et al.  Controlling TGF-beta signaling. , 2000, Genes & development.

[75]  S. Artavanis-Tsakonas,et al.  Crossing paths with Notch in the hyper-network. , 2007, Current opinion in cell biology.

[76]  M. Kim,et al.  Dickkopf 1 promotes regression of hair follicles. , 2012, The Journal of investigative dermatology.

[77]  J. Timmer,et al.  Supporting Online Material Material and Methods , 2022 .

[78]  J. Massagué,et al.  Controlling TGF-β signaling , 2000, Genes & Development.

[79]  Elaine Fuchs,et al.  Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. , 2005, Genes & development.

[80]  Sarah E. Millar,et al.  Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development , 2004, Development.

[81]  S. Millar,et al.  Molecular mechanisms regulating hair follicle development. , 2002, The Journal of investigative dermatology.

[82]  Elaine Fuchs,et al.  Scratching the surface of skin development , 2007, Nature.

[83]  J. Sundberg,et al.  The nude mouse skin phenotype: the role of Foxn1 in hair follicle development and cycling. , 2001, Experimental and molecular pathology.

[84]  Hans Clevers,et al.  Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4 , 1998, Nature Genetics.

[85]  J. Gordon,et al.  Genetic mosaic analysis indicates that the bulb region of coat hair follicles contains a resident population of several active multipotent epithelial lineage progenitors. , 2002, Developmental biology.

[86]  W. Van Hul,et al.  Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators. , 2002, Developmental biology.

[87]  M. Saffari,et al.  Differential expression analysis of balding and nonbalding dermal papilla microRNAs in male pattern baldness with a microRNA amplification profiling method , 2012, The British journal of dermatology.

[88]  David Schlessinger,et al.  The EDA gene is a target of, but does not regulate Wnt signaling. , 2002, Gene.

[89]  N. Mermod,et al.  Nuclear Factor I-C Regulates TGF-β-dependent Hair Follicle Cycling* , 2010, The Journal of Biological Chemistry.

[90]  Jian Li,et al.  Dedicated Epithelial Recipient Cells Determine Pigmentation Patterns , 2007, Cell.

[91]  M. Bonaguidi,et al.  Inhibition of BMP signaling in P-Cadherin positive hair progenitor cells leads to trichofolliculoma-like hair follicle neoplasias , 2011, Journal of Biomedical Science.

[92]  Chi-Chung Hui,et al.  Hedgehog signaling in development and cancer. , 2008, Developmental cell.

[93]  Pauline Chu,et al.  Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1 , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[94]  S. Artavanis-Tsakonas,et al.  Notch Signaling : Cell Fate Control and Signal Integration in Development , 1999 .

[95]  Raphael Kopan,et al.  gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. , 2004, Developmental cell.

[96]  C. Hui,et al.  Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development. , 2003, Genes & development.

[97]  M. Mikkola,et al.  Fgf20 governs formation of primary and secondary dermal condensations in developing hair follicles. , 2013, Genes & development.

[98]  F. Watt,et al.  The Vitamin D Receptor Is a Wnt Effector that Controls Hair Follicle Differentiation and Specifies Tumor Type in Adult Epidermis , 2008, PloS one.

[99]  K. Sekiguchi,et al.  Laminin-511 is an epithelial message promoting dermal papilla development and function during early hair morphogenesis. , 2008, Genes & development.

[100]  G. Martin,et al.  FGF5 as a regulator of the hair growth cycle: Evidence from targeted and spontaneous mutations , 1994, Cell.

[101]  Sarah E. Millar,et al.  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 , 2001, Mechanisms of Development.

[102]  J. Frank,et al.  Molecular pathways involved in hair follicle tumor formation: all about mammalian target of rapamycin? , 2009, Experimental dermatology.

[103]  Q. Lin,et al.  R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling , 2011, Proceedings of the National Academy of Sciences.

[104]  Jian Wang,et al.  Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. , 2006, Genes & development.

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

[106]  E. Epstein,et al.  Basal cell carcinomas arise from hair follicle stem cells in Ptch1(+/-) mice. , 2011, Cancer cell.

[107]  B. Hogan,et al.  Bone morphogenetic proteins: multifunctional regulators of vertebrate development. , 1996, Genes & development.

[108]  S. Aerts,et al.  Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation , 2012, Nature Cell Biology.

[109]  C. Kaufman,et al.  GATA-3: an unexpected regulator of cell lineage determination in skin. , 2003, Genes & development.

[110]  Jussi Taipale,et al.  Hedgehog: functions and mechanisms. , 2008, Genes & development.

[111]  S. R. Datta,et al.  Cellular survival: a play in three Akts. , 1999, Genes & development.

[112]  P. Dijke,et al.  New insights into TGF-β–Smad signalling , 2004 .

[113]  E. Fuchs,et al.  Paracrine TGF-β signaling counterbalances BMP-mediated repression in hair follicle stem cell activation. , 2012, Cell stem cell.

[114]  F. Watt,et al.  Transient activation of β-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours , 2004, Development.

[115]  Elaine Fuchs,et al.  Self-Renewal, Multipotency, and the Existence of Two Cell Populations within an Epithelial Stem Cell Niche , 2004, Cell.

[116]  M. Barbacid,et al.  RAS oncogenes: the first 30 years , 2003, Nature Reviews Cancer.

[117]  Hans Clevers,et al.  Lgr5 marks cycling, yet long-lived, hair follicle stem cells , 2008, Nature Genetics.

[118]  Desmond J. Tobin,et al.  NF-κB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth , 2006, Development.

[119]  E. Fuchs,et al.  Dynamics between Stem Cells, Niche, and Progeny in the Hair Follicle , 2011, Cell.

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

[121]  G. Johnson,et al.  Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases , 2002, Science.

[122]  Cathrin Brisken,et al.  Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis. , 2010, Genes & development.

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

[124]  Valerie Horsley,et al.  More than one way to skin . . . , 2008, Genes & development.

[125]  Pascal Schneider,et al.  Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression , 2007, Development.

[126]  M. Kim,et al.  Dihydrotestosterone-inducible IL-6 inhibits elongation of human hair shafts by suppressing matrix cell proliferation and promotes regression of hair follicles in mice. , 2012, The Journal of investigative dermatology.

[127]  B. Morgan,et al.  Epidermal stem cells arise from the hair follicle after wounding , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[128]  Hans Clevers,et al.  Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. , 2003, Genes & development.

[129]  E. Fuchs,et al.  The hair cycle , 2006, Journal of Cell Science.

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

[131]  F. Watt,et al.  Epidermal stem cells: an update. , 2006, Current opinion in genetics & development.

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

[133]  N. Perrimon,et al.  Notch modulates Wnt signalling by associating with Armadillo/β-catenin and regulating its transcriptional activity , 2005, Development.

[134]  Elaine Fuchs,et al.  Epidermal stem cells of the skin. , 2006, Annual review of cell and developmental biology.

[135]  Ken W. Y. Cho,et al.  Intracellular BMP signaling regulation in vertebrates: pathway or network? , 2001, Developmental biology.

[136]  S. Kato,et al.  Fibroblast growth factor 10 is required for proper development of the mouse whiskers. , 2003, Biochemical and biophysical research communications.

[137]  S. Söldner-Rembold,et al.  The first 30 years , 1983 .

[138]  Dorota Kurek,et al.  Transcriptome and phenotypic analysis reveals Gata3-dependent signalling pathways in murine hair follicles , 2007, Development.

[139]  E. Fearon,et al.  Transient activation of beta -catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. , 2003, Genes & development.

[140]  T. Suda,et al.  Wnt Signaling in the Niche , 2008, Cell.

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

[142]  C. Croce,et al.  MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma , 2008, Oncogene.

[143]  M. Koster,et al.  Roles of TGFβ signaling in epidermal/appendage development , 2003 .

[144]  T. Matsui,et al.  Evidence for autosomal dominant inheritance? , 1999, Diseases of the colon and rectum.

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

[146]  M. Birnbaum,et al.  Akt2 and SGK3 are both determinants of postnatal hair follicle development , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[147]  H. Clevers,et al.  Wnt signalling in stem cells and cancer , 2005, Nature.

[148]  G. Fishell,et al.  Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development , 2006, Nature Reviews Neuroscience.

[149]  I. Saadi,et al.  Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud-to-cap stage transition in tooth development , 2013, Development.

[150]  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.

[151]  M. Nemer,et al.  Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. , 2003, Developmental biology.

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

[153]  F. Watt,et al.  Role of integrins in regulating epidermal adhesion, growth and differentiation , 2002, The EMBO journal.

[154]  E. Fuchs,et al.  Defining the Epithelial Stem Cell Niche in Skin , 2004, Science.

[155]  C. Dickson,et al.  A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning , 2003, Development.

[156]  H Clevers,et al.  Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium. , 1999, The American journal of pathology.

[157]  T. Magnuson,et al.  Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. , 1997, The American journal of pathology.

[158]  R. Derynck,et al.  Smad-dependent and Smad-independent pathways in TGF-beta family signalling. , 2003, Nature.

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