| Budget Amount *help |
¥82,400,000 (Direct Cost: ¥82,400,000)
Fiscal Year 2009: ¥21,100,000 (Direct Cost: ¥21,100,000)
Fiscal Year 2008: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2007: ¥23,500,000 (Direct Cost: ¥23,500,000)
Fiscal Year 2006: ¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Research Abstract |
The development of mossy-fibre projecting precerebellar neurons (PCN) presents a classical example of tangential neuronal migration. Among the PCN, the pontine neurons follow a stereotypic anteroventral-directed pathway to form the pontine nuclei in the pons. The guidance mechanisms that determine the marginal migration of PCN and the anterior migration of pontine neurons are poorly understood. Here, we report that a chemokine SDF1 derived from the meningeal tissue regulates the migratory pathways of PCN. PCN are chemoattracted by the meningeal tissue, an effect that is mimicked by an SDF1 source. Analysis of knockout mice for the Sdf1 receptor Cxcr4 shows that both the marginal migration of PCN and the anterior migration of pontine neurons are disrupted. We further find that SDF1/CXCR4 signalling regulates these two processes cell-autonomously. As a result of disrupted neuronal migration, pontine nuclei formation was highly abnormal, with the presence of multiple ectopic pontine clusters posteriorly. The ectopic pontine clusters led to ectopic collateral branch formation from the corticospinal tract. Our results together demonstrate crucial roles for SDF1/CXCR4 in multiple aspects of PCN migration and highlight the deleterious consequence of derailed migration on proper nuclei formation. Furthermore, we provide the first in vivo evidence that pontine neurons themselves induce collateral branching from the corticospinal axons.
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