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Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish


The cerebellum is involved in motor coordination and motor learning. Granule cells are the major excitatory neurons in the cerebellum. It is largely unknown how the formation of cerebellar neural circuits, including the elaboration of granule cell axons, is controlled. We investigated a zebrafish mutant shiomaneki, in which some of the granule cells have abnormal axons. We identified collagen (col) 4a6 as the gene responsible for the mutant phenotype. Col4a6 forms a complex with Col4a5, which is a component of the basement membrane. We found that mutants of both col4a5 and col4a6 showed similar axonal abnormalities in both the granule cells and the retinal ganglion cells, and that the basement membrane structure surrounding the central nervous system was disrupted in these mutants. Furthermore, the abnormalities in granule cell axon formation were coupled with aberrant basement membrane structures in the col4a6 mutants. These data suggest that type IV collagen controls the axon formation of some types of neurons by establishing and/or maintaining the integrity of the basement membrane, which provides axons with the correct path to their targets. These findings may explain some aspects of a human disorder, Alport syndrome, which is caused by mutations in type IV collagen genes.


Vyšlo v časopise: Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005587
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005587

Souhrn

The cerebellum is involved in motor coordination and motor learning. Granule cells are the major excitatory neurons in the cerebellum. It is largely unknown how the formation of cerebellar neural circuits, including the elaboration of granule cell axons, is controlled. We investigated a zebrafish mutant shiomaneki, in which some of the granule cells have abnormal axons. We identified collagen (col) 4a6 as the gene responsible for the mutant phenotype. Col4a6 forms a complex with Col4a5, which is a component of the basement membrane. We found that mutants of both col4a5 and col4a6 showed similar axonal abnormalities in both the granule cells and the retinal ganglion cells, and that the basement membrane structure surrounding the central nervous system was disrupted in these mutants. Furthermore, the abnormalities in granule cell axon formation were coupled with aberrant basement membrane structures in the col4a6 mutants. These data suggest that type IV collagen controls the axon formation of some types of neurons by establishing and/or maintaining the integrity of the basement membrane, which provides axons with the correct path to their targets. These findings may explain some aspects of a human disorder, Alport syndrome, which is caused by mutations in type IV collagen genes.


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