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Involvement of platelet‐activating factor and LIS1 in neuronal migration
Author(s) -
Tokuoka Suzumi M.,
Ishii Satoshi,
Kawamura Noriko,
Satoh Mamoru,
Shimada Atsuyoshi,
Sasaki Shinji,
Hirotsune Shinji,
WynshawBoris Anthony,
Shimizu Takao
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02778.x
Subject(s) - platelet activating factor , receptor , microbiology and biotechnology , biology , platelet activating factor receptor , granule cell , cerebellum , chemistry , biochemistry , hippocampal formation , endocrinology , antagonist , dentate gyrus
Platelet‐activating factor (PAF, 1‐ O ‐alkyl‐2‐acetyl‐ sn ‐glycero‐3‐phosphocholine) is a biologically active lipid mediator. We have previously shown the expression of PAF receptor in neurons and microglia. PAF is produced in the brain from its precursor, and degraded by the enzyme PAF acetylhydrolase. LIS1 is a regulatory subunit of PAF acetylhydrolase, and is identical to a gene whose deletion causes the human neuronal migration disorder, type I lissencephaly. Indeed, Lis1 mutant mice display defects in neuronal migration and layering in vivo , and also in cerebellar granule cell migration in vitro . However, the roles of PAF and the PAF receptor in the neuronal migration remain to be determined. Here, we show that PAF receptor‐deficient mice exhibited histological abnormalities in the embryonic cerebellum. PAF receptor‐deficient cerebellar granule neurons migrated more slowly in vitro than wild‐type neurons, consistent with the observation that a PAF receptor antagonist reduced the migration of wild‐type neurons in vitro . Synergistic reduction of neuronal migration was observed in a double mutant of PAF receptor and LIS1. Unexpectedly, PAF affected the migration of PAF receptor‐deficient neurons, suggesting a receptor‐independent pathway for PAF action. The PAF receptor‐independent response to PAF was abolished in granule neurons derived from the double mutant mice. Thus, our results suggest that the migration of cerebellar granule cells is regulated by PAF through receptor‐dependent and receptor‐independent pathways, and that LIS1 is a pivotal molecule that links PAF action and neuronal cell migration both in vivo and in vitro .