Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch

The epidermis is a highly organized structure, the integrity of which is central to the protection of an organism. Development and subsequent maintenance of this tissue depends critically on the intricate balance between proliferation and differentiation of a resident stem cell population; however, the signals controlling the proliferation-differentiation switch in vivo remain elusive. Here, we show that mice carrying a homozygous missense mutation in interferon regulatory factor 6 (Irf6), the homolog of the gene mutated in the human congenital disorders Van der Woude syndrome and popliteal pterygium syndrome, have a hyperproliferative epidermis that fails to undergo terminal differentiation, resulting in soft tissue fusions. We further demonstrate that mice that are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show similar defects of keratinizing epithelia. Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process.     

Evolution of magma-poor continental margins from rifting to seafloor spreading

The rifting of continents involves faulting (tectonism) and magmatism, which reflect the strain-rate and temperature dependent processes of solid-state deformation and decompression melting within the Earth. Most models of this rifting have treated tectonism and magmatism separately, and few numerical simulations have attempted to include continental break-up and melting, let alone describe how continental rifting evolves into seafloor spreading. Models of this evolution conventionally juxtapose continental and oceanic crust. Here we present observations that support the existence of a zone of exhumed continental mantle, several tens of kilometres wide, between oceanic and continental crust on continental margins where magma-poor rifting has taken place. We present geophysical and geological observations from the west Iberia margin, and geological mapping of margins of the former Tethys ocean now exposed in the Alps. We use these complementary findings to propose a conceptual model that focuses on the final stage of continental extension and break-up, and the creation of a zone of exhumed continental mantle that evolves oceanward into seafloor spreading. We conclude that the evolving stress and thermal fields are constrained by a rising and narrowing ridge of asthenospheric mantle, and that magmatism and rates of extension systematically increase oceanward.