Zinc Finger Transcription Factors in Skeletal Development

Abstract

Cellular and molecular processes that regulate the development of skeletal tissues resemble those required for regeneration. Given the prevalence of degenerative skeletal disorders in an increasingly aging population, the molecular mechanisms of skeletal development must be understood in detail if novel strategies are to be developed in regenerative medicine. Research in this area over the past decade has revealed that cell differentiation is largely controlled at the level of gene transcription, which in turn is regulated by transcription factors. Transcription factors usually recognize and bind to specific DNA sequences in the promoter of target genes via characteristic DNA-binding domains. Although the gene family containing C2H2 zinc fingers as DNA-binding motifs is the largest family of transciptional regulators, with several hundred individual members in mammals, only a small but increasing number of zinc finger genes have been implicated in bone, cartilage, or tooth development. These zinc finger proteins (ZFPs) contain multiple structural motifs that require zinc to maintain their structural integrity and function. Interestingly, zinc deficiency is known to result in skeletal growth retardation and has been identified as a risk factor in the pathogenesis of osteoporosis. This review attempts to summarize our current state of knowledge regarding the role of ZFPs in the molecular regulation of skeletogenesis.