Regional Specification of Skin Appendage Phenotypes: Distinct Morphogen Profiles and Phenotypic Convergence During Feather Morphogenesis

Region-specific skin appendage phenotypes enable animals to meet diverse environmental and functional demands, yet the molecular basis of this specialization remains incompletely understood. Feathers vary markedly in size and shape across the avian body. Here, we investigate the relationship between regional feather phenotypes and morphogen signaling using bulk RNA sequencing, single-cell transcriptomics, spatial expression mapping, and in vivo functional perturbation. Adult chicken feathers from the scalp, neck, back, breast, forelimb, hindlimb, and tail each exhibit distinct morphogen signatures involving Wnt–Frizzled, FGF, IGF, and BMP pathway members. Elongated flight and sickle feathers shared an IGF-associated signature but differed in Wnt- and FGF-associated profiles, suggesting that similar phenotypes can arise through partially distinct molecular programs. Spatial mapping revealed region-specific Frizzled receptor expression within the proximal flight feather follicle. RCAS-mediated misexpression demonstrated that Wnt–Frizzled signaling is required for adult flight feather follicle regeneration and morphogenesis. Perturbation of individual Frizzled family members differentially affected flight feather follicle organization, cell survival, and feather filament elongation. Together, these findings show that region-specific feather phenotypes arise from combinations of core morphogen signaling modules that are differentially tuned by individual pathway components, providing a framework for understanding how a shared developmental toolkit generates diverse and convergent skin appendage phenotypes.