Analysis of the grainyhead-like genes in mammalian development and disease

This thesis describes research undertaken by Mr Michael Cangkrama, a PhD student at Monash University (Central Clinical School, Department of Medicine), investigating the unique and cooperative roles of the Grainyhead-like (Grhl) transcription factor family in mammalian epidermal development. Previous studies have defined critical roles of the three family members, Grhl1, -2 and -3 in embryonic epidermal morphogenis, in the context of skin development, wound repair, barrier formation and epidermal morphogenesis. Each of these transcription factors has distinct functions, which are presumably mediated through activation (or repression) of specific target genes. In the studies reported here, we have employed a variety of experimental approaches, including genetics, phylogenetic conservation, gene expression profiling, DNA-protein complex binding assays and other biochemical studies to identify key GRHL target genes for epidermal development and homeostasis in the adult. These studies are anticipated to have impact on human conditions in which barrier function is compromised, such as infant prematurity and atopic dermatitis, and will provide a scaffold for the development of therapeutic interventions for these disorders.