title: Sonic Hedgehog-signalling patterns the developing chicken comb as revealed by exploration of the pea-comb mutation.
abstract: The genetic basis and mechanisms behind the morphological variation observed throughout the animal kingdom is still relatively unknown. In the present work we have focused on the establishment of the chicken comb-morphology by exploring the Pea-comb mutant. The wild-type single-comb is reduced in size and distorted in the Pea-comb mutant. Pea-comb is formed by a lateral expansion of the central comb anlage into three ridges and is caused by a mutation in SOX5, which induces ectopic expression of the SOX5 transcription factor in mesenchyme under the developing comb. Analysis of differential gene expression identified decreased Sonic hedgehog (SHH) receptor expression in Pea-comb mesenchyme. By experimentally blocking SHH with cyclopamine, the wild-type single-comb was transformed into a Pea-comb-like phenotype. The results show that the patterning of the chicken comb is under the control of SHH and suggest that ectopic SOX5 expression in the Pea-comb change the response of mesenchyme to SHH signalling with altered comb morphogenesis as a result. A role for the mesenchyme during comb morphogenesis is further supported by the recent finding that another comb-mutant (Rose-comb), is caused by ectopic expression of a transcription factor in comb mesenchyme. The present study does not only give knowledge about how the chicken comb is formed, it also adds to our understanding how mutations or genetic polymorphisms may contribute to inherited variations in the human face.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Boije
authors.forename: Mohammad
authors.initials: M
authors.lastname: Harun-Or-Rashid
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Lee
authors.forename: Freyja
authors.initials: F
authors.lastname: Imsland
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bruneau
authors.forename: Agathe
authors.initials: A
authors.lastname: Vieaud
authors.forename: David
authors.initials: D
authors.lastname: Gourichon
authors.forename: Michèle
authors.initials: M
authors.lastname: Tixier-Boichard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bed'hom
authors.forename: Leif
authors.initials: L
authors.lastname: Andersson
authors.forename: Finn
authors.initials: F
authors.lastname: Hallböök
mesh_terms: D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000254:growth & development; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D003129:Comb and Wattles / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004475:Ectoderm / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D056726:Genetic Association Studies; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D055755:SOXD Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013194:Staining and Labeling; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D053823:Hedgehog Proteins; D055755:SOXD Transcription Factors; D014704:Veratrum Alkaloids; C000541:cyclopamine