Delta-like 1 regulates Bergmann glial monolayer formation during cerebellar development

Yuichi Hiraoka,Mai Nagaoka,Kohichi Tanaka,Okiru Komine,Katsuto Hozumi,Ning Bai

doi:10.1186/1756-6606-6-25

Abstract

BackgroundBergmann 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.ResultsIn 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.ConclusionThese 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.

Highlights

Bergmann glia (BG) are unipolar cerebellar astrocytes
Conditional ablation of Delta-like 1 (Dll1) leads to anatomical abnormalities in the adult cerebellum To study Dll1 function during cerebellar development, we inactivated Dll1 by using the Cre-loxP system with hGFAPCre mice, whereby the human Glial fibrillary acidic protein (GFAP) promoter directs the expression of Cre recombinase
The Dll1(loxP/loxP)/human glial fibrillary acidic protein (hGFAP)–Cre mice survived to adulthood and displayed no obvious abnormalities compared with controls

Summary

Introduction

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. We reported that Notch, Notch, and RBPj genes in the BG play crucial roles in the monolayer formation and morphogenesis of BG. It remains to be determined which ligand activates Nocth and Notch 2 on BG. Bergmann glia (BG) are unipolar cerebellar astroglial cells that have their soma in the Purkinje cell layer and extend radially arranged processes to the pial surface [1].

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Conclusion