The Role of the p35/cdk5 Kinase in Cortical Development

Abstract

Extensive studies on the mouse mutant reeler have revealed many of the fundamental characteristics of neocortical development (Caviness and Rakic 1978; Caviness 1982; Caviness et al. 1988). The finding of another spontaneously occurring mouse mutant, scrambler which exhibits nearly identical phenotypes with reeler suggests that the gene products mutated in the strains, mdab-1 and reelin, respectively, act in a common signaling pathway during cortical development (Sweet et al. 1996; Gonzalez et al. 1997; Howell et al. 1997; Sheldon et al. 1997; Ware et al. 1997; Rice et al. 1998). However, the vast complexity of events that must occur to set up the architecture of the cerebral cortex leads to the idea that multiple proteins are essential during cortical development. The p35/cdk5 kinase complex is one such molecular entity. Mouse knockouts of both p35 and cdk5 lead to disruptions of cortical lamination (Ohshima et al. 1996; Chae et al. 1997). Interestingly, the phenotype of the embryonic cerebral wall and adult neocortex in these mice is suggestive of but distinct from that of reeler or scrambler implying that a different essential function during cortical development may be disrupted in mice lacking p35 or cdk5 (Gilmore et al. 1998; Kwon and Tsai 1998).