Skin regional specification and higher-order HoxC regulation

• DOI: 10.1126/sciadv.ado2223
• Publication Date: 2025-03-21T18:22:12Z
• Authors: Shu-Man Hsieh Li; Ya-Chen Liang; Ting-Xin Jiang; Wen Chien Jea; Chih-Kuan Chen; Jiayi Lu; Daniel Núñez-León; Zhou Yu; Yung-Chih Lai; Randall B. Widelitz; Leif Andersson; Ping Wu; Cheng-Ming Chuong
• Keywords: Appendage; Integument; Integumentary system

The integument plays a critical role in functional adaptation, with macro-regional specification forming structures like beaks, combs, feathers, and scales, while micro-regional modifies skin appendage shapes. However, the molecular mechanisms remain largely unknown. Craniofacial displays dramatic diversity, exemplified by Polish chicken (PC) homeotic transformation of comb-to-crest caused 195–base pair (bp) duplication HoxC10 intron. Micro-C analyses show that HoxC-containing topologically associating domain (TAD) is normally closed scalp but open dorsal tail regions, allowing multiple long-distance contacts. In PC scalp, TAD open, resulting high HoxC expression. CRISPR-Cas9 deletion 195-bp reduces crest feather formation, misexpression alters sequence found only Archelosauria (crocodilians birds) not mammals. These findings suggest higher-order regulation cluster modulates gene expression, driving evolution adaptive integumentary appendages birds.