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

Neural development | May 3, 2012

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.

Pubmed ID: 22554084 RIS Download

Mesh terms: Animals | Base Sequence | Cell Cycle Proteins | Cell Differentiation | Cell Lineage | F-Box Proteins | Gene Expression Regulation, Developmental | Molecular Sequence Data | Oligodendroglia | Receptor, Notch1 | Sequence Alignment | Signal Transduction | Stem Cells | Transcription Factors | Ubiquitin-Protein Ligase Complexes | Ubiquitin-Protein Ligases | Zebrafish | Zebrafish Proteins

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Associated grants

  • Agency: NICHD NIH HHS, Id: T32 HD007502
  • Agency: NINDS NIH HHS, Id: NS046668
  • Agency: NINDS NIH HHS, Id: P30 NS048154

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Model organism database that serves as the central repository and web-based resource for zebrafish genetic, genomic, phenotypic and developmental data. Data represented are derived from three primary sources: curation of zebrafish publications, individual research laboratories and collaborations with bioinformatics organizations. Data formats include text, images and graphical representations. A wide-ranging collection of web-based search forms and tools facilitates access to integrated views of these data promoting analysis and scientific discovery. Recent additions to ZFIN include (i) enhanced access to images, (ii) genomic features, (iii) genome browser, (iv) transcripts, (v) antibodies and (vi) a community wiki for protocols and antibodies. ZFIN welcomes direct data submissions. If you would like to make your unpublished expression or phenotype data available to the community, you can submit this data to ZFIN using Phenote program. Additionally, data is downloadable.

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