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In vivo centrosome dynamics during neuronal migration and axonogenesis in the zebrafish cerebellum.

Vortrag: ISDN - Understanding the basic mechanisms of neurodevelopmental disorders, 6-9 June 2010, Estoril, Portugal. (2010)
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Underlying many neuronal migration disorders, such as lissencephalies, is a failure of the cell to properly orchestrate organelle dynamics. Here, the position of the centrosome ahead of the nucleus and in the direction of the forming axon is considered to be crucial for coordinating neuronal migration and determining the site of axonogenesis in differentiating neurons. We have generated cell type-specific multi-cistronic gene expression in the developing zebrafish cerebellum to monitor subcellular dynamics during neuronal migration. Using in vivo time-lapse analysis on transgenic zebrafish embryos, we have made several surprising findings: 1) Based on cell movements to and along the midbrain-hindbrain boundary, migration emanating from the zebrafish cerebellar rhombic lip was initially classified as a two-phase migration. Now organelle dynamics show that the first migratory phase represents interkinetic nuclear movements rather than true migration. 2) Neuronal migration usually occurs by a careful orchestration of organelle dynamics, in which the centrosome is believed to permanently lead migration by moving ahead of the nucleus. We find though that nucleokinetic migration in vivo does not involve a continuously leading centrosome. Instead the centrosome is regularly overtaken by the nucleus, questioning the current cell biological model of nucleokinesis. 3) Studies on explanted neurons have shown that the centrosome induces axonogenesis to occur from the nearest filopod. We demonstrate that in the developing cerebellum axonogenesis in early migrating neurons occurs at a clear distance to the centrosome and prior to centrosome-mediated nucleokinesis. These in vivo data reveal a new temporal orchestration of organelle dynamics during neuronal migration and axonogenesis.
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Publikationstyp Sonstiges: Vortrag
Konferenztitel ISDN - Understanding the basic mechanisms of neurodevelopmental disorders
Konferzenzdatum 6-9 June 2010
Konferenzort Estoril, Portugal