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The Journal of Neuroscience, July 5, 2006, 26(27):7293-7304; doi:10.1523/JNEUROSCI.0095-06.2006

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Development/Plasticity/Repair
FGF Signaling Mediates Regeneration of the Differentiating Cerebellum through Repatterning of the Anterior Hindbrain and Reinitiation of Neuronal Migration

Reinhard W. Köster¹ and Scott E. Fraser²

¹Gesellschaft für Strahlenforschung–National Research Center for Environment and Health, Institute of Developmental Genetics, 85764 Neuherberg-Munich, Germany, and ²Biological Imaging Center, Beckman Institute (139-74), California Institute of Technology, Pasadena, California 91125

Correspondence should be addressed to Reinhard Köster, Gesellschaft für Strahlenforschung–National Research Center for Environment and Health, Institute of Developmental Genetics, Ingolstädter Landstraße 1, 85764 Neuherberg-Munich, Germany. Email: Reinhard.Koester{at}gsf.de

To address the regenerative capability of the differentiating hindbrain, we ablated the cerebellum in wild-type and transgenic zebrafish embryos. These larvae showed no obvious locomotive malfunction several days after the ablation. Expression analysis and in vivo time-lapse recording in GFP (green fluorescent protein)-transgenic embryos indicate that cerebellar neuronal cells can regenerate from the remaining anterior hindbrain. The onset of regeneration is accompanied by repatterning within the anterior hindbrain. Inhibition of FGF signaling immediately after cerebellar ablation results in the lack of regenerating cerebellar neuronal cells and the absence of cerebellar structures several days later. Moreover, impaired FGF signaling inhibits the repatterning of the anterior hindbrain and the reexpression of rhombic lip marker genes soon after cerebellar ablation. This demonstrates that the hindbrain is highly plastic in recapitulating early embryonic differentiation mechanisms during regeneration. Moreover, the regenerating system offers a means to uncouple cerebellar differentiation from complex morphogenetic tissue rearrangements.

Key words: zebrafish; cerebellum; regeneration; plasticity; neuronal migration; bioimaging

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Received Jan. 10, 2006; revised May 29, 2006; accepted May 31, 2006.

Correspondence should be addressed to Reinhard Köster, Gesellschaft für Strahlenforschung–National Research Center for Environment and Health, Institute of Developmental Genetics, Ingolstädter Landstraße 1, 85764 Neuherberg-Munich, Germany. Email: Reinhard.Koester{at}gsf.de

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