In addition to its role in neuronal positioning during development, the secreted protein reelin regulates hippocampal dendritogenesis. Reelin acts by binding to the cell-surface receptors ApoER2 and VLDLR; this binding promotes the tyrosine phosphorylation of the intracellular receptor-bound protein Dab1. In turn, several other proteins – such as Crk and CrkL – can bind to phosphorylated Dab1; however, the role of Dab1 and its binding partners in dendrite formation has been unclear. Now Brian Howell and colleagues () show that Dab1, Crk and CrkL are important in reelin-regulated dendritogenesis after birth. Using a mouse cell line that expresses a conditional Dab1 allele, the authors inactivate Dab1 postnatally and show that the dendrite complexity of hippocampal pyramidal neurons is reduced. The authors go on to show that, in primary hippocampal neurons in culture, reelin increases dendrite length by approximately twofold, but knocking down both Crk and CrkL prevents reelin-stimulated dendritogenesis. Notably, neither axon length nor BDNF-regulated dendritogenesis are affected by the absence of Crk and CrkL. Thus, reelin stimulates hippocampal dendrite formation via a signalling pathway that includes Dab1, Crk and CrkL.
