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Delta-like 1 regulates Bergmann glial monolayer formation during cerebellar development
Yuichi Hiraoka1, Okiru Komine, Mai Nagaoka
1Laboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Background:
Bergmann glia (BG) are unipolar cerebellar astrocytes. The somata of mature BG reside in the Purkinje cell layer and extend radially arranged processes to the pial surface. BG have multiple branched processes, which enwrap the synapses of Purkinje cell dendrites. They migrate from the ventricular zone and align next to the Purkinje cell layer during development. Previously, we reported that Notch1, Notch2, and RBPj genes in the BG play crucial roles in the monolayer formation and morphogenesis of BG. However, it remains to be determined which ligand activates Nocth1 and Notch 2 on BG. Delta-like 1 (Dll1) is a major ligand of Notch receptors that is expressed in the developing cerebellum.
Results:
In this study, we used human glial fibrillary acidic protein (hGFAP) promoter-driven Cre-mediated recombination to delete Dll1 in BG. Dll1-conditional mutant mice showed disorganization of Bergmann fibers, ectopic localization of BG in the molecular layer and a reduction in the number of BG.
Conclusion:
These results suggest that Dll1 is required for the formation of the BG layer and its morphological maturation, apparently through a Notch1/2-RBPj dependent signaling pathway.
