LISSENCEPHALY GENE (LIS1) EXPRESSION IN THE CNS SUGGESTS A ROLE IN NEURONAL MIGRATION

Miller-Dieker lissencephaly syndrome (MDS) is a human developmental br ain malformation caused by neuronal migration defects resulting in abn ormal layering of the cerebral cortex. LIS1, the gene defective in MDS , encodes a subunit of brain platelet-activating factor (PAF) acetylhy drolase which inactivates PAF, a neuroregulatory molecule. We have iso lated murine cDNAs homologous to human LIS1 and mapped these to three different chromosomal loci (Lis1, Lis9 Lis4). The predicted sequences of murine Lis1 protein and its human homolog LIS1 are virtually identi cal. In the developing mouse and human, Lis1 and LIS1 genes were stron gly expressed in the cortical plate. In the adult mouse Lis1 transcrip ts were abundant in cortex and hippocampus. The direct correlation bet ween cortical defects in MDS patients and Lis1 expression in the murin e cortex suggest that the mouse is a model system suitable to study th e mechanistic basis of this intriguing genetic disease. Sequence data are deposited as L25108 for mouse Lis1 cDNA and L25109 for mouse Lis3- 4 cDNA.