Journal article
Cxcr7 Controls Neuronal Migration by Regulating Chemokine Responsiveness
JA Sánchez-Alcañiz, S Haege, W Mueller, R Pla, F Mackay, S Schulz, G López-Bendito, R Stumm, O Marín
Neuron | Published : 2011
Abstract
The chemokine Cxcl12 binds Cxcr4 and Cxcr7 receptors to control cell migration in multiple biological contexts, including brain development, leukocyte trafficking, and tumorigenesis. Both receptors are expressed in the CNS, but how they cooperate during migration has not been elucidated. Here, we used the migration of cortical interneurons as a model to study this process. We found that Cxcr4 and Cxcr7 are coexpressed in migrating interneurons, and that Cxcr7 is essential for chemokine signaling. Intriguingly, this process does not exclusively involve Cxcr7, but most critically the modulation of Cxcr4 function. Thus, Cxcr7 is necessary to regulate Cxcr4 protein levels, thereby adapting chemo..
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Awarded by Deutsche Forschungsgemeinschaft
Funding Acknowledgements
We thank A. Casillas, T. Gil, M. Perez, K. Schafer, A. Sorgenfrei, and H. Stadler for technical assistance; K. Campbell (Dlx5/6-Cre-IRES-Gfp) and N. Kesaris (Lhx6-Cre) for mouse strains; E. Arenas, F. Arenzana-Seisdedos, F. Guillemot, M. Penfold, M. Thelen, and V. Pachnis for plasmids and reagents; and V. Borrell for critically reading early versions of this paper. We are also thankful to members of the Mann, Rico, and Borrell labs for helpful discussions and comments. J.A.S-A. was supported by a fellowship from the FPU program of the Spanish Ministry of Science and Innovation (MICINN). This work was supported by grants from Spanish MICINN SAF2008-00770 and CONSOLIDER CSD2007-00023, and the EURYI scheme award (see www.esf.org/euryi) (to O.M), and by Federal State Sachsen-Anhalt with the European Fund For Regional Development (EFRE 2007-2013) and Deutsche Forschungsgemeinschaft (DFG) grant STU295/5-1 (to R.S).