CXCR4 and CXCR7 Have Distinct Functions in Regulating Interneuron Migration

Yanling Wang, Guangnan Li, Amelia Stanco, Jason E. Long, Dianna Crawford, Gregory B. Potter, Samuel J. Pleasure, Timothy Behrens, John L.R. Rubenstein

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    186 Scopus citations

    Abstract

    CXCL12/CXCR4 signaling is critical for cortical interneuron migration and their final laminar distribution. No information is yet available on CXCR7, a newly defined CXCL12 receptor. Here we demonstrated that CXCR7 regulated interneuron migration autonomously, as well as nonautonomously through its expression in immature projection neurons. Migrating cortical interneurons coexpressed Cxcr4 and Cxcr7, and Cxcr7-/- and Cxcr4-/- mutants had similar defects in interneuron positioning. Ectopic CXCL12 expression and pharmacological blockade of CXCR4 in Cxcr7-/- mutants showed that both receptors were essential for responding to CXCL12 during interneuron migration. Furthermore, live imaging revealed that Cxcr4-/- and Cxcr7-/- mutants had opposite defects in interneuron motility and leading process morphology. In vivo inhibition of Gα(i/o) signaling in migrating interneurons phenocopied the interneuron lamination defects of Cxcr4-/- mutants. On the other hand, CXCL12 stimulation of CXCR7, but not CXCR4, promoted MAP kinase signaling. Thus, we suggest that CXCR4 and CXCR7 have distinct roles and signal transduction in regulating interneuron movement and laminar positioning.

    Original languageEnglish (US)
    Pages (from-to)61-76
    Number of pages16
    JournalNeuron
    Volume69
    Issue number1
    DOIs
    StatePublished - Jan 13 2011

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    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Wang, Y., Li, G., Stanco, A., Long, J. E., Crawford, D., Potter, G. B., Pleasure, S. J., Behrens, T., & Rubenstein, J. L. R. (2011). CXCR4 and CXCR7 Have Distinct Functions in Regulating Interneuron Migration. Neuron, 69(1), 61-76. https://doi.org/10.1016/j.neuron.2010.12.005