The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a 
substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) 
facilitates polyubiquitination and subsequent degradation of various proteins 
such as Notch, cyclin E, c-Myc and c-Jun. Fbw7 is highly expressed in the 
nervous system and controls neural stem cell differentiation and apoptosis via 
Notch and c-Jun during embryonic development (Hoeck et al., 2010). Fbw7 deletion 
in the neural lineage is perinatal lethal and thus prohibits studying the role 
of Fbw7 in the adult nervous system. fbw7 mRNA is highly expressed in the 
postnatal brain and to gain insights into the function of Fbw7 in postnatal 
neurogenesis we analysed Fbw7 function in the cerebellum. We generated 
conditional Fbw7-knockout mice (fbw7(∆Cb)) by inactivating Fbw7 specifically in 
the cerebellar anlage. This resulted in decreased cerebellar size, reduced 
Purkinje cell number and defects in axonal arborisation. Moreover, 
Fbw7-deficient cerebella showed supranumeral fissures and aberrant progenitor 
cell migration. Protein levels of the Fbw7 substrates Notch1 and N-terminally 
phosphorylated c-Jun were upregulated in fbw7(∆Cb) mice. Concomitant deletion of 
c-Jun, and also the junAA knock-in mutation which specifically abrogates c-Jun 
N-terminal phosphorylation, rescued Purkinje cell numbers and arborisation in 
the fbw7(∆Cb) background. Taken together these data demonstrate that Fbw7 is 
essential during cerebellar development, and identify N-terminally 
phosphorylated c-Jun as an important substrate of SCF(Fbw7) during neurogenesis.