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Axonal/Dendritic Growth and Circuit Formation

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

Basement membrane structure is important for axogenesis of cerebellar granule cells

  • P1-104
  • 竹内 未紀 / Miki Takeuchi:1,2,3,4 
  • 1:名古屋大生物機能開発利用セ / Bioscience and Biotechnology Center, Nagoya University 2:理研発生・再生科学総合研セ / RIKEN Center for Developmental Biology, Hyogo, Japan 3:国立遺伝研 / National Institute of Genetics, Shizuoka, Japan 4:岡崎統合バイオサイエンスセ / Okazaki Institute for Integrative Bioscience, Aichi, Japan 

The cerebellum forms in the dorsal part of the most anterior hindbrain and functions in motor learning. Granule cells are the major glutamatergic neurons in the cerebellum. Granule cells in the anterior lobes of the cerebellum (valvula and corpus cerebelli) send their axons to the dendrites of Purkinje cells, whereas granule cells in the caudolateral lobes (eminentia granularis and lobus caudalis cerebelli) send them to the dendrites of crest cells, Purkinje-like cells, in the dorsal hindbrain. We isolated transgenic zebrafish lines which express a modified Gal4 or a fluorescent protein in granule cells. Imaging with these lines demonstrated that granule cells in the anterior and caudolateral lobes took different developmental processes in their axogenesis. To understand the mechanisms that control the axogenesis of granule cells, we studied a zebrafish mutant shiomaneki, the larvae of which showed shortened and/or mistargeted axons of the granule cells in the caudolateral lobe. Positional cloning revealed that the shiomaneki gene encodes Col4a6, which is a subunit of type IV collagen and serves as a component of the basement membrane (BM). Both Col4a5 and Col4a6 mutants showed the same abnormal axogenesis of cerebellar granule cells and retinal ganglion cells, indicating that the complex of Col4a5 and Col4a6 controls axogenesis of these neurons. The BM structure was disorganized in Col4a5 and Col4a6 mutants. Furthermore we found similar phenotypes in the mutants of Fibronectin1a and Integrin &alpha5, implying that Fibronectin-Integrin signaling is required for integrity of the BM, which is subsequently utilized by the granule cells for their axogenesis. Our data suggest that the interaction of the granule cell axons with the BM plays an important role in axogenesis of the granule cells. We shall also report our progress toward identification of guidance system(s) that control axon pathfinding of the granule cells by RNA sequencing.

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