2006 Fiscal Year Final Research Report Summary
Molecular mechanisms of dendrite branching in CNS neurons
| Project/Area Number |
16300098
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | RIKEN |
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Principal Investigator |
KENGAKU Mineko RIKEN, Laboratory for Neural Cell Polarity, Team Leader, 神経細胞極性研究チーム, チームリーダー (10303801)
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| Project Period (FY) |
2004 – 2006
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| Keywords | DNER / CNS neurons / dendrite / selective transport / clathrin / synapse / purkinie cells |
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| Research Abstract |
Towards the goal to clarity the mechanisms of patterning of dendrite trees in developing CNS neurons, we conducted three projects as follows.
(1) Molecular bases of dendrite arborization in CNS neurons
(a) We analyzed the function of dendrite-specific transmembrane protein DNER and found that it acts as a bona fide ligand for Notch in the CNS. DNER regulates morphological differentiation of Bergmann glia and neuronal differentiation in the retina and telencephalon. (b) We found that Sonic hedgehog induced spine formation in dendrites of cultured Purkinje cells and hippocampal neurons. Sonic hedgehog receptor Smo bound to PSD95 via the cytoplasmic tail, suggesting Shh signal is activated at the postsynaptic membrane. (c) We identified Sept3 as a component of heteromeric polymers accumulating in the presynaptic membrane. We generated mice deficient of the Sept3 gene and found that Sept3 is dispensable for normal neuronal development
(2) Selective sorting of somatodendritic plasma membrane molecule DNER.
We demonstrated that the somatodendritic targeting of DNER requires clathrin-dependent-and independent-endocytosis. Thus, mechanisms downstream of direct sorting pathways from the TGN are required for polarization of a somatodendritic membrane protein.
(3) Development of imaging techniques for analysis of dendrite formation.
We developed a method to analyze the tertiary structure of developing Purkinje cell dendrite by using a GFP-carrying adeno-associated virus (AAV) vector. We identified conformational remodeling of Purkinje cell dendritic arbors to flatten multiplanar dendrites in a monolayer in late postnatal stages.
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