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The Alternative Splicing Regulator Nova2 Constrains Vascular Erk Signaling to Limit Specification of the Lymphatic Lineage
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- Baek, Sungmin (author)
- Univ Queensland, Inst Mol Biosci, Div Genom Dev & Dis, Brisbane, Qld 4073, Australia
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- Oh, Tae Gyu (author)
- Univ Queensland, Inst Mol Biosci, Div Cell Biol & Mol Med, Brisbane, Qld 4073, Australia
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- Secker, Genevieve (author)
- Univ South Australia, Ctr Canc Biol, Adelaide, SA, Australia;SA Pathol, Adelaide, SA 5000, Australia
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- CELL PRESS, 2019
- 2019
- English.
- In: Developmental Cell. - : CELL PRESS. - 1534-5807 .- 1878-1551. ; 49:2, s. 279-292
- Journal article (peer-reviewed)
Abstract
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- The correct assignment of cell fate within fields of multipotent progenitors is essential for accurate tissue diversification. The first lymphatic vessels arise from pre-existing veins after venous endothelial cells become specified as lymphatic progenitors. Prox1 specifies lymphatic fate and labels these progenitors; however, the mechanisms restricting Prox1 expression and limiting the progenitor pool remain unknown. We identified a zebrafish mutant that displayed premature, expanded, and prolonged lymphatic specification. The gene responsible encodes the regulator of alternative splicing, Nova2. In zebrafish and human endothelial cells, Nova2 selectively regulates pre-mRNA splicing for components of signaling pathways and phosphoproteins. Nova2-deficient endothelial cells display increased Mapk/Erk signaling, and Prox1 expression is dynamically controlled by Erk signaling. We identify a mechanism whereby Nova2-regulated splicing constrains Erk signaling, thus limiting lymphatic progenitor cell specification. This identifies the capacity of a factor that tunes mRNA splicing to control assignment of cell fate during vascular differentiation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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