December 14, 2006
Four years ago, a team of NIDCR grantees and colleagues isolated a gene involved in causing Van der Woude syndrome, the most common of the syndromic forms of cleft lip and palate. Amid the good news, the scientists predicted that further study of the gene, called intereferon regulatory factor (Irf6), would likely reveal a series of important clues into mammalian and thus human development. In the November issue of the journal Nature Genetics, the NIDCR grantees and their colleagues report on the latest developmental clue to be teased out of Irf6. The scientists found that mice with deficient amounts of the Irf6 protein in utero are born with abnormal skin, limb, and craniofacial development. Their analyses indicated that the primary defect involved keratinocytes, the major cell type of the epidermis, suggesting the Irf6 protein is necessary to regulate their proper differentiation and proliferation. According to the authors, their discovery links for the first time an IRF family member to epidermal development. As they noted, “The new roles for a member of the IRF family expand the repertoire of IRF functions from stress response into development but suggest a bridge that spans these apparently disparate functions.” Read more about this paper by Ingraham et al.
In the same issue of Nature Genetics, another group of NIDCR grantees report independently and simultaneously that Irf6 “is a key determinant of the keratinocyte proliferation-differentiation switch.” The finding is based on work with mice that carried a missense mutation in both copies of the Irf6 gene in utero. Read more about this paper by Richardson et al.