title: Local inhibitory action of BMPs and their relationships with activators in feather formation: implications for periodic patterning.
abstract: The formation of periodic patterns is fundamental in biology. Theoretical models describing these phenomena have been proposed for feather patterning; however, no molecular candidates have been identified. Here we show that the feather tract is initiated by a continuous stripe of Shh, Fgf-4, and Ptc expression in the epithelium, which then segregates into discrete feather primordia that are more strongly Shh and Fgf-4 positive. The primordia also become Bmp-2 and Bmp-4 positive. Bead-mediated delivery of BMPs inhibits local feather formation in contrast with the activators, SHH and FGF-4, which induce feather formation. Both FGF-4 and SHH induce local expression of Bmp-4, while BMP-4 suppresses local expression of both. FGF-4 also induces Shh. Based on these findings, we propose a model that involves (1) homogeneously distributed global activators that define the field, (2) a position-dependent activator of competence that propagates across the field, and (3) local activators and inhibitors triggered in sites of individual primordia that act in a reaction-diffusion mechanism. A computer simulation model for feather pattern formation is also presented.
authors.affiliation: School of Medicine, University of Southern California, HMR 204, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Jung
authors.forename: P H
authors.initials: PH
authors.lastname: Francis-West
authors.forename: R B
authors.initials: RB
authors.lastname: Widelitz
authors.forename: T X
authors.initials: TX
authors.lastname: Jiang
authors.forename: S
authors.initials: S
authors.lastname: Ting-Berreth
authors.forename: C
authors.initials: C
authors.lastname: Tickle
authors.forename: L
authors.initials: L
authors.lastname: Wolpert
authors.forename: C M
authors.initials: CM
authors.lastname: Chuong
mesh_terms: D000818:Animals; D019521:Body Patterning; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005164:Factor IX / Q000378:metabolism; D005241:Feathers / Q000196:embryology*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D008954:Models, Biological; D010507:Periodicity; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012867:Skin / Q000196:embryology*; D014018:Tissue Distribution; D015534:Trans-Activators; D016212:Transforming Growth Factor beta
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D051519:Fibroblast Growth Factor 4; D053823:Hedgehog Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D005164:Factor IX