The London Research Institute hosts a number of conferences throughout the year and has extensive seminar schedules as part of its education programme.
Highlighted Paper: The F-box protein Fbw7 is required for cerebellar development.
Submitted by hawkes07 on Thu, 10/11/2011 - 09:57
The Mammalian Gentics Lab headed by Axel Behrens published the following paper in Development Biology.
Jandke A, Da Costa C, Sancho R, Nye E, Spencer-Dene B, Behrens A. The F-box protein Fbw7 is required for cerebellar development. Dev Biol. 2011; 358(1):201-12. (Abstract).
Fbw7 is part of the SCF ubiquitin ligase complex and mediates the degradation of a variety of substrates, among them Notch and phosphorylated form of the transcription factor c-Jun. We and others have shown that Fbw7 acts as a tumour suppressor and that Fbw7 is required for normal brain development where it controls neuronal differentiation.
To further investigate Fbw7 function in the nervous system we have generated mice that lack Fbw7 specifically in the cerebellum. The cerebellum is organised in layers of different neurons that are supported by glia cells. While the deletion of Fbw7 does not alter the overall layering, the cerebellum is smaller and the number and morphology of Purkinje cells is changed. Moreover we found that the Fbw7 substrates phospho-c-Jun and Notch accumulate in the cerebellum.
We hypothesized that the increased levels of phospho-c-Jun are responsible for the observed defects and that removal of c-Jun should rescue normal brain development. Indeed, when we additionally removed c-Jun from the cerebellum or used a c-Jun mutant that cannot be phosphorylated, we observed a return to an almost normal morphology with some aspects remaining altered.
This suggests regulation of phospho-c-Jun levels by Fbw7 is essential for cerebellar development.
Figure Legend: Cerebellar Fbw7 deletion reduces overall cerebellar size in Purkinje cell numbers, impairs Purkinje cell arborisation and causes activation of glia cells. Brains of seven day old control and Fbw7 deleted mice fbw7ΔCb are stained with Purkinje cell markers Calbindin (left panel) and with GFAP (right panel). The dendritic arborisation (white arrows) is reduced and glia cell activation is enhanced in fbw7ΔCb cerebella. |
