084
Expression of MSX1 and Keratins 14 and 19 After Human Fetal Digit Tip Amputation in Vitro

Abstract

We have developed a human fetal digit model of response to tip amputation to simulate the clinical phenomenon of digit tip regrowth or regeneration in children. We reported previously that younger estimated gestational age (EGA) digits respond to tip amputation with several layers of cells covering the phalangeal anlage, compared to older digits where such coverage comprises fewer cell layers or is absent. The proximal cut end of excised digits does not demonstrate such a response. We report here that the transcription repressor MSX1 is expressed beneath the developing nailfield in younger human fetal digits (57 to 67 days EGA), as has been shown in the mouse, and that cells expressing MSX1 are found at the digit tip by 4 days postamputation. Further, expression of keratins K14 and K19 is found, suggesting reforming of an epithelium. These findings are consistent with the mouse model of digit tip regeneration where MSX1‐expressing cells are hypothesized to migrate to the amputation site and reconstitute the missing tip, and with the general observation that a wound epidermis is required for either regeneration or wound healing. 57 d EGA digits; left, MSX1 expression, control; left center, MSX1 and center, K19 expression, day 4 posttip amputation; right center, MSX1 and right, K19 expression, day 7 postamputation