Evolutionarily conserved, alternative splicing of reelin during brain development

Reelin is the protein defective in reeler mutant mice and plays a pivotal r ole in brain development. However, some uncertainties remain about the rela tionship between reelin and the reeler phenotype. It is generally believed that reelin, secreted by specific neuronal types such as Cajal-Retzius cell s, acts at short distance via the extracellular matrix on target neurons, t he response of which requires the Dab1 gene product. However, the pattern o f reelin expression in some structures such as olfactory bulb, retina, and spinal cord suggests that the protein might be endowed with different funct ions. In the present study, we identify two uncommon, evolutionarily conser ved splicing events in the 3' part of the transcript that result in differe nt forms of the protein. First, a 6-nucleotide, brain-specific microexon is skipped in about 10% of reelin RNA. In addition, an alternative polyadenyl ation event involving 10-25% of reelin mRNA results in secretion of a trunc ated protein lacking the terminal, highly basic stretch. This alternative r eelin is generally expressed in the same cells as the major form; but is al most undetectable in retina and spinal cord. Both alternative splicing even ts are present in mouse, rat;, and man, suggesting that the corresponding r eelin forms are functionally important. (C) 1999 Academic Press.