The SDF‐1/CXCR4 pathway and the development of the cerebellar system

TO Vilz, B Moepps, J Engele, S Molly… - European Journal of …, 2005 - Wiley Online Library
TO Vilz, B Moepps, J Engele, S Molly, DR Littman, K Schilling
European Journal of Neuroscience, 2005Wiley Online Library
Mice deficient for the chemokine receptor CXCR4 show premature translocation of granule
cell neuroblasts from their germinal zone into the nascent cerebellum [Y.‐R. Zuo et al.(1998)
Nature, 393, 595–599]. Here, we used CXCR4‐null mice to analyse the early development
of cerebellar cortical inhibitory interneurons and pontine neurons which, in the adult, are
synaptically integrated with granule cells. Cortical inhibitory interneuronal precursors
normally invade the cerebellar anlage of CXCR4‐deficient mice, but their dispersal is …
Abstract
Mice deficient for the chemokine receptor CXCR4 show premature translocation of granule cell neuroblasts from their germinal zone into the nascent cerebellum [Y.‐R. Zuo et al. (1998)Nature, 393, 595–599]. Here, we used CXCR4‐null mice to analyse the early development of cerebellar cortical inhibitory interneurons and pontine neurons which, in the adult, are synaptically integrated with granule cells. Cortical inhibitory interneuronal precursors normally invade the cerebellar anlage of CXCR4‐deficient mice, but their dispersal is impeded by dislocated foci of proliferating granule cells, from which they are excluded. This is reminiscent of the strict exclusion of inhibitory interneuronal precursors from the superficial external granule cell layer. As inhibitory interneuronal precursors readily mingle with post‐mitotic granule cells both in wild‐type and CXCR4‐null mice, these findings indicate that the developmentally regulated interactions between granule and inhibitory interneuronal precursors are independent of SDF‐1/CXCR4 signalling. In contrast, the transit of pontine neurons from the rhombic lip through the anterior extramural stream to the basilar pons is disrupted in CXCR4‐deficient animals. Migrating pontine neurons express CXCR4, and in CXCR4‐null animals these cells are found displaced deep into the brainstem. Consequently, nascent pontine nuclei in CXCR4‐deficient animals are hypoplastic. Moreover, they fail to express plexin D1, suggesting that SDF‐1/CXCR4 signalling may also impinge on axon guidance critical to the orderly formation of granule cell mossy fibre afferents.
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