title: Wnt3a gradient converts radial to bilateral feather symmetry via topological arrangement of epithelia.
abstract: The evolution of bilaterally symmetric feathers is a fundamental process leading toward flight. One major unsolved mystery is how the feathers of a single bird can form radially symmetric downy feathers and bilaterally symmetric flight feathers. In developing downy feather follicles, barb ridges are organized parallel to the long axis of the feather follicle. In developing flight-feather follicles, the barb ridges are organized helically toward the anterior region, leading to the fusion and creation of a rachis. Here we discover an anterior-posterior molecular gradient of wingless int (Wnt3)a in flight but not downy feathers. Global inhibition of the Wnt gradient transforms bilaterally symmetric feathers into radially symmetric feathers. Production of an ectopic local Wnt3a gradient reoriented barb ridges toward the source and created an ectopic rachis. We further show that the orientation of the Wnt3a gradient is dictated by the dermal papilla (DP). Swapping DPs between wing covert and breast downy feathers demonstrates that both feather symmetry and molecular gradients are in accord with the origin of the DP. Thus the fates of feather epidermal cells are not predetermined through some molecular codes but can be modulated. Together, our data suggest feathers are shaped by a DP--> Wnt gradient-->helical barb ridge organization-->creation of rachis-->bilateral symmetry sequence. We speculate diverse feather forms can be achieved by adjusting the orientation and slope of molecular gradients, which then shape the topological arrangements of feather epithelia, thus linking molecular activities to organ forms and novel functions.
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Zhicao
authors.initials: Z
authors.lastname: Yue
authors.forename: Ting-Xin
authors.initials: TX
authors.lastname: Jiang
authors.forename: Randall Bruce
authors.initials: RB
authors.lastname: Widelitz
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Chuong
mesh_terms: D000818:Animals; D001717:Birds; D019521:Body Patterning; D002645:Chickens; D004848:Epithelium / Q000033:anatomy & histology* / Q000473:pathology*; D005241:Feathers / Q000033:anatomy & histology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D021621:Imaging, Three-Dimensional; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D008953:Models, Anatomic; D008954:Models, Biological; D009024:Morphogenesis; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000196:embryology; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein
chemical_list: D051153:Wnt Proteins; D060508:Wnt3 Protein