TY - JOUR
T1 - CXCR4 and CXCR7 Have Distinct Functions in Regulating Interneuron Migration
AU - Wang, Yanling
AU - Li, Guangnan
AU - Stanco, Amelia
AU - Long, Jason E.
AU - Crawford, Dianna
AU - Potter, Gregory B.
AU - Pleasure, Samuel J.
AU - Behrens, Timothy
AU - Rubenstein, John L.R.
N1 - Funding Information:
We thank Marc von Zastrow and Mark Penfold for helpful discussions and reagents. This work was supported by the research grants to J.L.R.R. from Citizens United for Research in Epilepsy (C.U.R.E.), Nina Ireland, Larry L. Hillblom Foundation, Weston Havens Foundation, and NIMH R37 MH049428; to Y.W. from C.U.R.E Rhode Island Award from the Epilepsy Foundation; and to S.J.P. from K02 MH074985 and R01 MH077694. Timothy W. Behrens and Jason E. Long are full-time employees of Genentech, Inc. Dianna Crawford is a full-time employee of Amgen, Inc.
PY - 2011/1/13
Y1 - 2011/1/13
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2010.12.005
DO - 10.1016/j.neuron.2010.12.005
M3 - Article
C2 - 21220099
AN - SCOPUS:78650956554
VL - 69
SP - 61
EP - 76
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -