Fbxw7 regulates Notch to control specification of neural precursors for oligodendrocyte fate

Neural Development

Bruce Appel¹  Christina A Kearns²  Julia L Snyder² 

[1] University of Colorado School of Medicine, MS 8108, Aurora, CO, 80045, USA;Departments of Pediatrics and Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA

关键词: Zebrafish;    Neural precursor;    Myelin;    Oligodendrocyte;    Glia;    Notch;   

Others  :  807684
DOI  :  10.1186/1749-8104-7-15

 received in 2012-01-03, accepted in 2012-05-03,  发布年份 2012

【 摘 要 】

Background

In the developing vertebrate nervous system elevated levels of Notch signaling activity can block neurogenesis and promote formation of glial cells. The mechanisms that limit Notch activity to balance formation of neurons and glia from neural precursors are poorly understood.

Results

By screening for mutations that disrupt oligodendrocyte development in zebrafish we found one allele, called vu56, that produced excess oligodendrocyte progenitor cells (OPCs). Positional cloning revealed that the vu56 allele is a mutation of fbxw7, which encodes the substrate recognition component of a ubiquitin ligase that targets Notch and other proteins for degradation. To investigate the basis of the mutant phenotype we performed in vivo, time-lapse imaging, which revealed that the increase in OPC number resulted from production of extra OPCs by ventral spinal cord precursors and not from changes in OPC proliferation or death. Notch signaling activity was elevated in spinal cord precursors of fbxw7 mutant zebrafish and inhibition of Notch signaling suppressed formation of excess OPCs.

Conclusion

Notch signaling promotes glia cell formation from neural precursors in vertebrate embryos. Our data indicate that Fbxw7 helps attenuate Notch signaling during zebrafish neural development thereby limiting the number of OPCs.

【 授权许可】

   
2012 Snyder et al.; licensee BioMed Central Ltd.

【 图 表 】

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