Twist2 contributes to skin regeneration and hair follicle formation in mouse fetuses

Abstract

Abstract Unlike adult mammalian wounds, early embryonic mouse skin wounds completely regenerate and heal without scars. Analysis of the underlying molecular mechanism will provide insights into scarless wound healing. Twist2 is an important regulator of hair follicle formation and biological patterning; however, whether it plays a role in skin or skin appendage regeneration remains unclear. We aimed to elucidate Twist2 expression and role in fetal wound healing. ICR mouse fetuses were surgically wounded at embryonic days 13 (E13), E15, and E17, and Twist2 expression in tissue samples from these fetuses was evaluated via in situ hybridization, immunohistochemical staining, and reverse transcription-quantitative polymerase chain reaction. Twist2 was upregulated in the dermis of E13 wound margins but downregulated in E15 and E17 wounds. Twist2 knockdown at E13 left visible marks at the wound site, inhibited regeneration, and resulted in defective follicle formation. Twist2-knockdown dermal fibroblasts lacked the ability to undifferentiate. Furthermore, twist2 hetero knockout mice (Twist+/-) formed visible scars, even at E13, where all skin structures, including texture, should regenerate. Thus, Twist2 expression correlated with skin texture formation and hair follicle defects in late mouse embryos. These findings may help develop a therapeutic strategy to reduce scarring and promote hair follicle regeneration.