The pathogenesis of craniosynostosis in the fetus

Craniosynostosis occurs in approximately 1:2000 live births. It may affect the coronal, sagittal, metopic and lambdoid sutures in isolation or in combination. Although non-syndromic synostoses are more common, over 150 genetic syndromes have been identified. Recent advances in genetic mapping have linked chromosomal mutations with craniosynostotic syndromes. Despite the identification of these genetic mutations, the fundamental biomolecular mechanisms mediating cranial suture biology remain unknown. Today, many laboratories are investigating murine cranial suture biology as a model for human cranial suture development and fusion. Normal murine cranial suture biology is very complex, but evidence suggests that the dura mater provides the biomolecular blueprints (e.g. the soluble growth factors), which guide the fate of the pleuripotent osteogenic fronts. While our knowledge of these dura-derived signals has increased dramatically in the last decade, we have barely begun to understand the fundamental mechanisms that mediate cranial suture fusion or patency. Interestingly, recent advances in both premature human and programmed murine suture fusion have revealed unexpected results, and have generated more questions than answers.

Gene therapy of scarring: a lesson learned from fetal scarless wound healing

Cutaneous wounding in adult humans and higher vertebrate animals results in scar formation. In contrast, both human and animal fetuses, at early gestational ages, exhibit skin wound healing without scarring. This distinction suggests that the repair of adult wounds by skin regeneration, rather than by fibrosis, may be achieved if adult wounds can be modified to mimic the healing process of fetal wounds. The development of gene therapy offers the possibility to specifically enhance or block the gene expression of cytokines and extracellular molecules, and thus convert adult wound healing into a healing process more similar to tissue regeneration. This article reviews the characteristics of fetal wound repair focusing on cytokine profiles and the inflammatory response to dermal injury. Also included are new developments in gene transfer techniques as well as their application in wound healing. Finally, the authors propose possible strategies of wound gene therapy, to reduce wound scarring and to promote tissue regeneration.