Nonneuronal roles for the reelin signaling pathway

The reelin signaling pathway has been established as an important regulator of cell migration during development of the central nervous system, and disruptions in reelin signaling alter the positioning of many types of neurons. Reelin is a large extracellular matrix glycoprotein and governs cell migration through activation of multiple intracellular signaling events by means of the receptors ApoE receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR), and the intracellular adaptor protein Disabled-1 (Dab1). Earlier studies reported expression of reelin in nonneuronal tissues, but the functions of this signaling pathway outside of the nervous system have not been studied until recently. A large body of evidence now suggests that reelin functions during development and disease of multiple nonneuronal tissues. This review addresses recent advances in the field of nonneuronal reelin signaling. Developmental Dynamics 246:217-226, 2017. © 2016 Wiley Periodicals, Inc.