PREDOMINANT LOCALIZATION OF THE LIS FAMILY OF GENE-PRODUCTS TO CAJAL-RETZIUS CELLS AND VENTRICULAR NEUROEPITHELIUM IN THE DEVELOPING HUMAN CORTEX

Mutations that perturb neuronal migration provide important biological clues that can lead to an understanding of the role of specific cells and molecules in the formation of the cortex. The human neuronal migr ation disorder, Miller-Dieker lissencephaly, results from a hemideleti on of LIS-1, which encodes a subunit of a brain platelet-activating fa ctor acetylhydrolase. The cellular localization of the LIS-1 gene prod uct in human fetal brain and its normal role in neuronal migration hav e yet to be determined. LIS-1 belongs to a family of genes that have i dentical coding sequences (LIS-1 [chromosome 17] and LIS-2 [chromosome 2]). In the brain, LIS-1 is the more abundant gene as determined by N orthern blot analysis. Using antibodies raised against 2 epitopes of t he LIS-1/LIS-2 protein sequence, we have localized the LIS family of g ene products in the developing human brain to the Cajal-Retzius cells, some subplate neurons, thalamic neurons, the ventricular neuroepithel ium, and at later gestational ages, to the ependyma. Therefore, LIS-1 bears some resemblance to reelin, the gene product involved in the cor tical mouse mutant reeler, in that Cajal-Retzius cells demonstrate imm unolocalization. However, unlike reelin, LIS proteins are expressed no t only in the Cajal Retzius cells, but also in the ventricular neuroep ithelium, suggesting a potential role for this structure in neuronal m igration.