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

Summary: Abstract Body: Understanding organ size regulation is a fundamental biological question. Bird feathers of the same bird exhibit incremental length changes which are important for their function and present a good model to study the mechanism of organ size. This study examines how feather length is controlled in chickens in short contour versus long sickle feathers. We also examined Phoenix chicken variant known for their exceptionally long sickle feathers. We observed the length can be controlled by growth rate and growth period. At cellular level, the collar bulge stem cell zones differ in size from small to long feathers. IGF and FGF are initially highly expressed, while BMP and WIF1 levels rise as growth concludes. Functional assays indicate that IGF and FGF signaling promote feather elongation through tyrosine kinase receptor pathways. Single-cell RNA sequencing (scRNA-seq) reveals that keratinocyte differentiation occurs more rapidly in short contour feathers compared to long sickle feathers. In Phoenix chickens, the exceptionally long main sickle feathers possess specialized stem cell zones with increased Delta-like 1 (DLL1) expression and expanded intermediate-layer cell clusters. These clusters exhibit dynamic interactions involving Notch/DLL, YAP1, and Wnt signaling within progenitor zones in the proximal follicle. Perturbation experiments resulting in shorter feather phenotypes arrested at various stages provide insights into the versatile regulatory mechanisms governing feather length. The work suggest that growth rate relies on IGF/FGF signaling, while growth period relies on the duration in which collar progenitor cells are active. The topological arrangement of progenitor cells in collar region set up a cellular platform for Yap / Notch/ Dl1 circuit to work as sensor and actuator of length control. This research enhances our understanding of feather length control and offers potential avenues for manipulating length of skin appendages. Ping Wu¹, Federico Bocci², Chris Juarez², Arthur Lander², Qing Nie², Cheng Ming Chuong¹ 1. University of Southern California, Los Angeles, CA, United States. 2. University of California Irvine, Irvine, CA, United States. Stem Cell Biology, Tissue Regeneration and Wound Healing