THE REELER GENE ENCODES A PROTEIN WITH AN EGF-LIKE MOTIF EXPRESSED BYPIONEER NEURONS

We have identified a strong candidate cDNA for the mouse reeler gene. This 5 kb transcript encodes a 99.4 kD protein consisting of 881 amino acids and possessing two EGF-like motifs. We assayed two independent mutant alleles - 'Jackson reeler', which has a deletion of the entire gene, and 'Orleans reeler' which exhibits a 220 bp deletion in the ope n reading frame, including the second EGF-like motif and resulting in a frame shift. In situ hybridization reveals that the transcript is de tected exclusively in the pioneer neurons which guide neuronal cell mi gration along the radial array. Our findings offer an explanation for how the reeler mutant phenotype causes a disturbance of the complex ar chitecture of the neuronal network.