Hoxc13 Polyglycine Repeat Gain-Of-Function Drives Mammalian Integument Evolution By Altering Targeted Genes And Interactions

May 2026 in “ Research Square ”

Guanghao Yang, Chaoyong Huang, Miao Yu, Wei Li, Dubala Wu, Chun Li, Sile Hu, Jianghong Wu

Hoxc13 polyglycine repeat hair development integument evolution hair follicle morphogenesis Wnt signaling pathway gene regulatory networks protein conformation Cdx1 downstream signaling gene expression hair growth skin evolution hair follicles Wnt pathway gene networks protein structure

Studysummary This research reports that the polyG fragment within the Hoxc13 protein alters its gene regulatory functions, which could have influenced mammalian hair evolution by affecting pathways related to hair follicle development.

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This study examines the role of the polyglycine (polyG) repeat in the Hoxc13 protein, which is essential for hair development and mammalian integument evolution. Researchers compared the normal Hoxc13-W protein with the polyG-deleted Hoxc13-S protein in cashmere goats, finding that Hoxc13-W identified significantly more DNA-binding peaks (12,679) than Hoxc13-S (3,634). The polyG fragment enhances Hoxc13's binding to genes involved in hair follicle morphogenesis and cycling, particularly in the Wnt signaling pathway. This suggests that the polyG fragment modulates gene regulatory networks, contributing to the evolution of mammalian skin appendages like hair. The study also highlights the polyG fragment's role in protein conformation and interaction with other proteins, such as Cdx1, affecting downstream signaling and gene expression.

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