MODULATION OF THE HUMAN HOMEOBOX GENES PRX-2 AND HOXB13 IN SCARLESS FETAL WOUNDS

Scarless healing of cutaneous wounds occurs in humans during the first two trimesters of development, but by birth all wounds are repaired w ith scar formation. To search for transcriptional regulatory genes tha t might mediate fetal tissue regeneration, we surveyed homeobox gene e xpression in proliferating fetal fibroblasts and in wounded and unwoun ded skin, Two novel human homeobox genes, PRX-2 and HOXB13, were ident ified that were differentially expressed during fetal versus adult wou nd healing. Both genes were predominantly expressed in proliferating f etal fibroblasts and developing dermis, and PRX-2 was downregulated in adult skin. In a model of scarless fetal skin regeneration, PRX-2 exp ression was strongly increased compared with unwounded skin and the si gnal was localized to the wounded dermis, the site of scarless repair. Conversely, in adult skin weak epidermal PRX-2 expression was observe d, mRNA levels were not increased by wounding, and no dermal expressio n was detected. HOXB13 expression was decreased in wounded fetal tissu e relative to unwounded fetal controls or wounded adult skin. Thus bot h HOXB13 and PRX-2 are expressed in patterns consistent with roles in fetal skin development and cutaneous regeneration.