Reelin/dab1 signaling in the developing cerebral cortex

Mice lacking the cytoplasmic adapter protein Dab1 (Disabled homolog-1) display histological defects in the central nervous system (CNS) that are essentially indistinguishable from those observed in the reeler mouse. Dab1 is expressed in virtually all Reelin-responsive cells and is rapidly phosphorylated in response to Reelin application. The finding of a near identity in phenotype, coupled with a direct biochemical response to Reelin, has raised great interest in understanding Dab1 function, both as an exemplar of an adapter protein with a profound phenotypic contribution, and as a means of decoding mechanisms of Reelin signaling. What has emerged from these studies is a surprisingly complex picture of Dab1 at the genomic, mRNA, protein, and functional levels. This chapter will summarize some of the key features of Dab1, and its role as a transducer of the Reelin signal in the developing cerebral cortex.