Final Activity Report Summary - GLI3 LIMB PATTERNING (Setting-up a patterning system: the regulation and temporal changes in functioning of the transcriptional regulator gli3 ...)
As this lethality has precluded the study of the functions of Gli3 during per- and postnatal development and adult life in more detail, we have generated a mouse model that allows to inactivate Gli3 in a temporally and/or spatially controlled manner either during embryogenesis or after birth. Using this so-called conditional Gli3 allele, we are now dissecting the functions and temporal requirement of this SHH gatekeeper during limb and brain development in mouse embryos and in SHH-dependent tumorigenesis after birth.
Using a novel technique (RMCE), we have also generated additional alterations in the Gli3 locus, that allow us to detect and purify the GLI3 containing transcriptional complexes from intact embryonic and adult tissues. This systems biology-type approach in combination with cell-biochemistry aims to analyse of the functions and interactions of GLI3 during embryogenesis, tumourigenesis and in adult tissues and stem cells.