Flightless I deficiency enhances wound repair by increasing cell migration and proliferation.

Wound healing disorders are a therapeutic problem of increasing clinical importance involving substantial morbidity, mortality, and rising health costs. Our studies investigating flightless I (FliI), a highly conserved actin-remodelling protein, now reveal that FliI is an important regulator of wound repair whose manipulation may lead to enhanced wound outcomes. We demonstrate that FliI-deficient + /- mice are characterized by improved wound healing with increased epithelial migration and enhanced wound contraction. In contrast, FliI-overexpressing mice have significantly impaired wound healing with larger less contracted wounds and reduced cellular proliferation. We show that FliI is secreted in response to wounding and that topical application of antibodies raised against the leucine-rich repeat domain of the FliI protein (FliL) significantly improves wound repair. These studies reveal that FliI affects wound repair via mechanisms involving cell migration and proliferation and that FliI might represent an effective novel therapeutic factor to improve conditions in which wound healing is impaired.

Structure and expression of the ovine Hoxc-13 gene.

HOXC-13 has an important role in controlling hair formation through regulating keratin differentiation-specific genes. In this study, we describe the isolation and characterisation of the Hoxc-13 gene from sheep wool follicles and its expression in the skin. We show that the gene organisation of ovine Hoxc-13 is similar to other homeobox genes of the Abd-B type I Homeobox class with two exons split by an intron next to the homeobox. The gene spans 7.5 kilobases (kb) and has a relatively large intron, which divides an open reading frame of 2361 nucleotides. The predicted ovine Hoxc-13 protein of 330 amino acids has over 97% sequence identity with the human and mouse proteins. A second novel transcript was identified, which could produce a truncated Hoxc-13 protein lacking 15 amino acids from the N-terminus. A positionally conserved Hoxc-13 binding site in the Hoxc-13 proximal promoters of sheep, human, mouse and newt suggests that Hoxc-13 expression is autoregulatory. Positionally conserved motifs for LEF-1 and Whn/Foxn1 suggest that Hoxc-13 may be a downstream target of these transcription factors known to regulate hair growth. In addition to expression in the follicle, we detected Hoxc-13 in cells of the blood sinus surrounding vibrissal follicles and in scattered cells in the upper dermis of the skin. Thus, in addition to a role in controlling transcription of hair keratins, Hoxc-13 may have other roles in skin function.