Regulation of feather length: FGF/IGF signaling and NOTCH/YAP modulation of progenitor cell topology

The regulation of organ size is a fundamental biological question. This study investigates how feather length is regulated in chickens. We found that collar bulge stem cell zones vary in size: main sickle > lesser sickle > contour feathers. During growth, IGF and FGF9 signaling are highly expressed, while BMP, WIF1, and FGF18 increase toward growth termination. Functional assays show that insulin-like growth factor/fibroblast growth factor signaling promotes feather elongation via tyrosine kinase receptor signaling. Single-cell RNA sequencing analysis reveals accelerated differentiation of keratinocytes in short contour feathers compared to long sickle feathers. In Phoenix chickens, superlong main sickle feathers exhibit specialized stem cell zones with enhanced DLL1 expression and expanded intermediate-layer cell clusters with dynamic interactions involving NOTCH1/DLL1, YAP1, and WNT signaling in progenitor zones in the proximal follicle. Perturbation experiments induce short feather phenotypes arrested at various stages, shedding light on versatile regulatory mechanisms and paving the way for functional control of diverse feather lengths.