DNER as key molecule for cerebellar maturation.

Notch signaling plays an important role in the process of cell-fate assignation during nervous system development. DNER is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats and is expressed in somatodendritic regions. In vitro studies demonstrated that DNER mediates Notch signaling by cell-cell interaction. In the cerebellum, DNER is abundantly expressed in Purkinje cells and moderately in granule cells. DNER-knockout mice showed motor discoordination. The mutant cerebellum showed morphological impairments of Bergmann glia and multiple innervation between climbing fibers and Purkinje cells. Moreover, glutamate clearance at the synapses between parallel fibers and Purkinje cells was significantly weakened, and the expression of GLAST, a glutamate transporter in Bergmann glia, was reduced in the mutant cerebellum. Therefore, DNER contributes to the morphological and functional maturation of Bergmann glia via the Notch signaling pathway, and is essential for precise cerebellar development.