“CRL4COP1 ubiquitination complex as a balancer of early odontogenesis”
Cullin-RING ubiquitin ligase (CRL) complexes have been heavily studied in connection to cancer progression but there is limited evidence about their physiological roles. One of the exceptions is disruption of limb development by thalidomide induced by inhibition of CRL4 complex via regulation of Fgf8 (Ito et al., 2010). Notably, Fgf8 expressing population is essential also for development of tooth primordia and we found CRL4 genes to be specifically expressed within odontognic epithelium. We further identified COP1 as a substrate binding protein which can bind ETS transcription factors, downstream targets of Fgf pathway, and unveiled that conditional deletion of CRL4 genes severly affects size and morphology of molar primordia and future teeth.