Functional analysis of Lrig1 and Lrig3 in adult epidermal stem cell self-renewal. (360G-Wellcome-088454_Z_09_Z)
My studies of Lrig1, a negative regulator of receptor tyrosine kinases, have demonstrated a link between stem cell self-renewal and receptor activity. I will establish whether the effect of Lrig1 on stem cell behaviour is a general feature of receptor activation and Lrig family members. Lrig3 will be assessed for its role in vivo in epidermal homeostasis and the effect of receptor tyrosine kinase inhibition and activation will be investigated in vitro. Regulation of receptor kinase activity is e ssential for homeostasis and these aims will help us understand disease progression. I have demonstrated that Lrig1 defines murine interfollicular epidermal stem cells. I will use expression profiling to define the unique properties of Lrig1 expressing cells and perform lineage analysis to establish their role in homeostasis and repair. This will require the generation of a Lrig1::dsRed-IRES-CreERT2 reporter mouse. My studies demonstrate that Lrig1 governs stem cell quiescence. To address whe ther hyperplasia in Lrig1 KO mice is caused by increased stem cell contribution, I will perform in vivo clone assays. The combination of these aims will define the role of Lrig1 and interfollicular epidermal stem cells. This will provide a unique tool to understand how these cells participate in epidermal disorders.
£970,388 23 Jun 2009