Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2006-6-14
pubmed:abstractText
Hair follicles are spaced apart from one another at regular intervals through the skin. Although follicles are predominantly epidermal structures, classical tissue recombination experiments indicated that the underlying dermis defines their location during development. Although many molecules involved in hair follicle formation have been identified, the molecular interactions that determine the emergent property of pattern formation have remained elusive. We have used embryonic skin cultures to dissect signaling responses and patterning outcomes as the skin spatially organizes itself. We find that ectodysplasin receptor (Edar)-bone morphogenetic protein (BMP) signaling and transcriptional interactions are central to generation of the primary hair follicle pattern, with restriction of responsiveness, rather than localization of an inducing ligand, being the key driver in this process. The crux of this patterning mechanism is rapid Edar-positive feedback in the epidermis coupled with induction of dermal BMP4/7. The BMPs in turn repress epidermal Edar and hence follicle fate. Edar activation also induces connective tissue growth factor, an inhibitor of BMP signaling, allowing BMP action only at a distance from their site of synthesis. Consistent with this model, transgenic hyperactivation of Edar signaling leads to widespread overproduction of hair follicles. This Edar-BMP activation-inhibition mechanism appears to operate alongside a labile prepattern, suggesting that Edar-mediated stabilization of beta-catenin active foci is a key event in determining definitive follicle locations.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-10431241, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-10431242, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-10918306, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-11703920, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-11780064, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-11809808, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-11841536, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-11851869, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-12015971, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-12048258, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-12134160, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-12526755, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-12692542, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-14623234, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-15031115, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-15617562, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-15714560, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-16087884, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-16277556, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-2203463, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-7763240, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-7958926, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-8696334, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-8752214, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-9281334, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-9359753, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-9527877, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-9768360, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-9799834, http://linkedlifedata.com/resource/pubmed/commentcorrection/16769906-9845363
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9075-80
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:16769906-Animals, pubmed-meshheading:16769906-Body Patterning, pubmed-meshheading:16769906-Bone Morphogenetic Protein 4, pubmed-meshheading:16769906-Bone Morphogenetic Protein 7, pubmed-meshheading:16769906-Bone Morphogenetic Proteins, pubmed-meshheading:16769906-Edar Receptor, pubmed-meshheading:16769906-Embryo, Mammalian, pubmed-meshheading:16769906-Female, pubmed-meshheading:16769906-Gene Expression Regulation, Developmental, pubmed-meshheading:16769906-Hair Follicle, pubmed-meshheading:16769906-In Situ Hybridization, pubmed-meshheading:16769906-Male, pubmed-meshheading:16769906-Mice, pubmed-meshheading:16769906-Mice, Transgenic, pubmed-meshheading:16769906-Morphogenesis, pubmed-meshheading:16769906-Receptors, Ectodysplasin, pubmed-meshheading:16769906-Receptors, Tumor Necrosis Factor, pubmed-meshheading:16769906-Signal Transduction, pubmed-meshheading:16769906-Skin, pubmed-meshheading:16769906-Tissue Culture Techniques, pubmed-meshheading:16769906-Transcription, Genetic, pubmed-meshheading:16769906-Transforming Growth Factor beta
pubmed:year
2006
pubmed:articleTitle
Generation of the primary hair follicle pattern.
pubmed:affiliation
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't