Fig. 5.

Fine-tuning Reelin signaling by Dab1 alternative splicing during development—a model. Early in development, alternative splicing produces Dab1 isoforms that exclude exons 7 and/or 8. These isoforms show absent or reduced associations with SH2 domain-containing proteins, leading to absent or attenuated activation of downstream pathways. As a result, cells expressing these isoforms may have a compromised ability to detach and translocate in response to Reelin. As development proceeds, inclusion of exons 7 and 8 in Dab1 generates the canonical Dab1 isoform that recruits the full set of SH2 domain-containing proteins, resulting in full activation of downstream signaling. Cells expressing the canonical Dab1 isoform are able to detach and translocate in response to Reelin, resulting in the inside-out lamination that is characteristic of the cortical plate. Gray indicates reduced interaction; magenta indicates normal interaction