Cell-autonomous inactivation of the reelin pathway impairs adult neurogenesis in the hippocampus

Catia M. Teixeira, Michelle M. Kron, Nuria Masachs, Helen Zhang, Diane C. Lagace, Albert Martinez, Isabel Reillo, Xin Duan, Carles Bosch, Lluis Pujadas, Lucas Brunso, Hongjun Song, Amelia J. Eisch, Victor Borrell, Brian W. Howell, Jack M. Parent, Eduardo Soriano

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Adult hippocampal neurogenesis is thought to be essential for learning and memory, and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of Disabled-1, an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain-of-function and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adultgenerated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus, and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)12051-12065
Number of pages15
JournalJournal of Neuroscience
Volume32
Issue number35
DOIs
StatePublished - Aug 29 2012

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Cell-autonomous inactivation of the reelin pathway impairs adult neurogenesis in the hippocampus'. Together they form a unique fingerprint.

  • Cite this

    Teixeira, C. M., Kron, M. M., Masachs, N., Zhang, H., Lagace, D. C., Martinez, A., Reillo, I., Duan, X., Bosch, C., Pujadas, L., Brunso, L., Song, H., Eisch, A. J., Borrell, V., Howell, B. W., Parent, J. M., & Soriano, E. (2012). Cell-autonomous inactivation of the reelin pathway impairs adult neurogenesis in the hippocampus. Journal of Neuroscience, 32(35), 12051-12065. https://doi.org/10.1523/JNEUROSCI.1857-12.2012