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Involvement of platelet-activating factor and LIS1 in neuronal migration
Suzumi M Tokuoka1, Satoshi Ishii, Noriko Kawamura
1Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, CREST of JST, Tokyo 113-0033, Japan.
The European Journal of Neuroscience
|August 13, 2003
Summary
Platelet-activating factor (PAF) regulates neuronal migration via receptor-dependent and independent pathways. The protein LIS1 is crucial for linking PAF
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Platelet-activating factor (PAF) is a lipid mediator expressed in the brain.
- The PAF receptor is present in neurons and microglia.
- LIS1, a subunit of PAF acetylhydrolase, is linked to neuronal migration disorders.
Purpose of the Study:
- To investigate the roles of PAF and its receptor in neuronal migration.
- To elucidate the function of LIS1 in PAF-mediated neuronal migration.
Main Methods:
- Generation and analysis of PAF receptor-deficient mice.
- In vitro migration assays of cerebellar granule neurons.
- Assessment of neuronal migration in double mutants (PAF receptor and LIS1).
Main Results:
- PAF receptor deficiency caused cerebellar histological abnormalities and slower neuronal migration.
- PAF receptor antagonist reduced wild-type neuronal migration.
- Synergistic defects in neuronal migration were observed in double mutants.
- PAF influenced neuronal migration independently of its receptor, a pathway dependent on LIS1.
Conclusions:
- PAF regulates cerebellar granule cell migration through both receptor-dependent and -independent pathways.
- LIS1 is a key molecule connecting PAF signaling to neuronal cell migration.