Smad in skin /appendage development

Baylor College Of Medicine, Houston TX

Investigators

Linked publications & trials

Abstract

The transforming growth factor beta (TGFbeta) superfamily plays an important role in epidermal/appendage development. The major signaling mediators for this superfamily. The major signaling mediators for this superfamily are Smads. Germline deletions of individual Smad isoforms results in early embryonic lethality in most cases. The phenotypes of these Smad knockout mice indicates that Smads play pivotal roles in embryogenesis primarily via TGFbeta-dependent pathways. Our preliminary data have shown that Smads are highly expressed in the epidermis during skin development. Taken together, we hypothesize that Smads may play important roles in skin development. This proposal will assess the roles of individual Smads in skin development. To determine the cooperative effects of multiple pathways of the TGFbeta superfamily, Smad7, which blocks TGFbeta, activin and BMP signaling, will be inducibly to delete Smad2 (for TGF/activin signaling) and Smad5 (for BMP signaling) during skin development. These transgenic/knockout mice will provide in vivo models that circumvent the neonatal or embryonic lethality resulting from the conventional transgenic over- expression or the germline knockout of individual Smad genes. These models will also be used to identify interactions of Smads that are critical for epidermal development will be screened after the acute induction of Smad7 over-expression or deletion of Smad2 or Smad5 in the skin of these transgenic/knockout mice. The proposed studies will address unsolved questions regarding the roles and mechanisms of the TGFbeta superfamily in skin development. In addition, animal models generated in this proposal may identify Smad functions that are independent of the TGFbeta superfamily signaling. These studies will also determine whether Smads can be used as targets for therapeutic approaches for skin diseases resulting from developmental defects.