Reelin Regulates Neuronal Progenitor Migration in Intact and Epileptic Hippocampus

By Chao Gong, Tsu-Wei Wang, Holly S. Huang, J. Parent. 2007

227 citations recorded by the source corpus.

Dentate granule cell (DGC) neurogenesis persists throughout life in the mammalian hippocampal dentate gyrus and increases after epileptogenic insults. The DGC layer in human and experimental mesial temporal lobe epilepsy (mTLE) often shows abnormal dispersion and the appearance of hilar-ectopic DGCs. In the pilocarpine mTLE model, hilar-ectopic DGCs arise as a result of an aberrant chain migration of neural progenitors. Reelin is a secreted migration guidance cue that persists in the adult rodent and human hippocampus. We tested the hypothesis that loss of Reelin in the epileptic dentate gyrus leads to aberrant chain migration of DGC precursors. We found that interneuron subsets typically lost in human and experimental mTLE express Reelin, and DGC progenitors express the downstream Reelin signaling molecule Disabled 1 (Dab1). Prolonged seizures decreased Reelin immunoreactivity in the adult rat dentate gyrus and increased Dab1 expression in hilar-ectopic neuroblasts. Exogenous Reelin increased detachment of chain-migrating neuroblasts in dentate gyrus explants, and blockade of Reelin signaling increased chain migration. These findings suggest that Reelin modulates DGC progenitor migration to maintain normal DGC integration in the neonatal and adult mammalian dentate gyrus. Loss of Reelin expression in the epileptic adult hippocampus, moreover, likely contributes to ectopic chain migration and aberrant integration of newborn DGCs.

Subfields: Cancer Research, Developmental Neuroscience, Molecular Biology

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Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “In the dentate gyrus, reelin signaling prevents new neurons from migrating into the hilus region; loss of reelin expression from local interneurons after pilocarpine-induced seizures may explain the ectopic hilar localization of new granule cells (Gong et al., 2007).”
Development of neural stem cell in the adult brain. (2008, background): “Reelin signaling prevents new neurons from migrating into the hilus region; loss of reelin expression from local interneurons after pilocarpineinduced seizures may explain the ectopic hilar localization of new granule cells [33].”
Modification of hippocampal circuitry by adult neurogenesis (2012, background): “On the other hand, loss of Reelin expression from local interneurons in an animal model of seizures results in the ectopic hilar localization of newborn granule cells (Gong et al., 2007).”
Mechanisms and functional implications of adult neurogenesis. (2008, unknown): “Signaling through the Reelin pathway may be involved in such regulation (Gong et al., 2007).”