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    foxc1 is required for embryonic head vascular smooth muscle differentiation in zebrafish

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    Authors
    Whitesell, Thomas R.
    Chrystal, Paul W.
    Ryu, Jae-Ryeon
    Munsie, Nicole
    Grosse, Ann S.
    French, Curtis R.
    Workentine, Matthew L.
    Li, Rui
    Zhu, Lihua Julie
    Waskiewicz, Andrew
    Lehmann, Ordan J.
    Lawson, Nathan D.
    Childs, Sarah J.
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    UMass Chan Affiliations
    Program in Molecular Medicine
    Department of Molecular, Cell, and Cancer Biology
    Document Type
    Journal Article
    Publication Date
    2019-06-11
    Keywords
    CRISPR
    RNA-Seq transcriptome
    Vascular smooth muscle cell
    Zebrafish
    acta2
    foxc1b
    Cell Biology
    Developmental Biology
    Musculoskeletal System
    
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    Link to Full Text
    https://doi.org/10.1016/j.ydbio.2019.06.005
    Abstract
    Vascular smooth muscle of the head derives from neural crest, but developmental mechanisms and early transcriptional drivers of the vSMC lineage are not well characterized. We find that in early development, the transcription factor foxc1b is expressed in mesenchymal cells that associate with the vascular endothelium. Using timelapse imaging, we observe that foxc1b expressing mesenchymal cells differentiate into acta2 expressing vascular mural cells. We show that in zebrafish, while foxc1b is co-expressed in acta2 positive smooth muscle cells that associate with large diameter vessels, it is not co-expressed in capillaries where pdgfrbeta positive pericytes are located. In addition to being an early marker of the lineage, foxc1 is essential for vSMC differentiation; we find that foxc1 loss of function mutants have defective vSMC differentiation and that early genetic ablation of foxc1b or acta2 expressing populations blocks vSMC differentiation. Furthermore, foxc1 is expressed upstream of acta2 and is required for acta2 expression in vSMCs. Using RNA-Seq we determine an enriched intersectional gene expression profile using dual expression of foxc1b and acta2 to identify novel vSMC markers. Taken together, our data suggests that foxc1 is a marker of vSMCs and plays a critical functional role in promoting their differentiation.
    Source

    Dev Biol. 2019 Jun 11. pii: S0012-1606(19)30209-X. doi: 10.1016/j.ydbio.2019.06.005. [Epub ahead of print] Link to article on publisher's site

    DOI
    10.1016/j.ydbio.2019.06.005
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/44372
    PubMed ID
    31199900
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ydbio.2019.06.005
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