Year: 2017
Type: report
Abstract: During neocortical development, excitatory neurons generated in the ventricular zone migrate towards the pial surface.Neurons stop migrating when they reach at just beneath the marginal zone, then following neurons pass through preceding neurons to establish superficial layers, resulting in a so-called "inside-out" pattern.This layer formation is regulated by several signaling cascades, including the Reelin signaling.Reelin is a glycoprotein mainly secreted by Cajal-Retzius neurons in the marginal zone, and known to function via its lipoprotein receptors, apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (Vldlr), and the cytoplasmic adaptor protein disabled 1 (Dab1).The Vldlr single mutant shows invasion of migrating neurons into the MZ without defect in the radial migration, whereas reeler mice lacking the Reelin protein, Apoer2/Vldlr double knockout mice and Dab1 mutants show severe migration defects with roughly inverted formation of the cortical layers, suggesting that Vldlr has specific roles for termination of neuronal migration beneath the MZ.However, precise mechanisms by which Reelin signaling controls the termination of neuronal migration remains unclear.Here, to gain insight into the role of Vldlrmediated Reelin signaling during cortical development, we examined the migratory behavior of Vldlr-deficient neurons in the developing brain.Stage-specific labeling of newborn neurons revealed that the both the earlier-born and later-born neurons ectopically invaded the MZ in the Vldlr mutants and that Vldlr-deficiency significantly impaired dendrite outgrowth in the MZ.Rescue experiments showed that Vldlr has a cell-autonomous function and that adhesion molecules function downstream of Vldlr.These results suggest that Vldlr controls the proper termination of radial migration during cortical development.
Author: 廣田, ゆき
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7145746736