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Impaired cerebellar functions in mutant mice lacking DNER
Akira Tohgo1, Mototsugu Eiraku, Taisuke Miyazaki
1Department of Medical Chemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Molecular and Cellular Neurosciences
|November 22, 2005
Summary
Developmental Netrin-Responsive protein (DNER) is crucial for cerebellar development. Its absence in knockout mice impairs motor coordination and causes abnormal brain structure, highlighting DNER's role in cell communication and maturation.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- DNER is a transmembrane protein with EGF repeats, highly expressed in cerebellar Purkinje cells (PCs).
- DNER acts as a novel Notch ligand, facilitating cell-cell communication.
Purpose of the Study:
- To investigate the role of DNER in cerebellar development and function.
- To elucidate the mechanisms by which DNER influences cerebellar morphogenesis and synaptic activity.
Main Methods:
- Generation and analysis of DNER knockout mice.
- Behavioral tests (fixed bar, rota-rod) to assess motor coordination.
- Histochemical and electrophysiological analyses of cerebellar tissue.
- Assessment of glutamate transporter (GLAST) levels.
Main Results:
- DNER knockout mice exhibit motor discoordination and cerebellar morphological defects, including abnormal fissure organization.
- PCs in mutant mice show persistent multiple climbing fiber innervations.
- Glutamate clearance at parallel fiber-Purkinje cell synapses is impaired.
- Reduced GLAST protein levels in the cerebellum of DNER knockout mice.
Conclusions:
- DNER is essential for the proper functional and morphological maturation of the cerebellum.
- DNER signaling is involved in stimulating Bergmann glia (BG) maturation through intercellular communication.
- DNER plays a critical role in precise cerebellar development.