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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.
Pubmed ID: 31014480 RIS Download
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Java toolset for working with next generation sequencing data in the BAM format.
View all literature mentionsSoftware tool to detect differential alternative splicing events from RNA-Seq data. Calculates P value and false discovery rate that difference in isoform ratio of gene between two conditions exceeds given user defined threshold. Can automatically detect and analyze alternative splicing events corresponding to all major types of alternative splicing patterns. Handles replicate RNA-Seq data from both paired and unpaired study design.
View all literature mentionsSoftware application for assembling of RNA-Seq alignments into potential transcripts. It enables improved reconstruction of a transcriptome from RNA-seq reads. This transcript assembling and quantification program is implemented in C++ .
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets prox1a in the nucleus of lymphatic endothelial cells
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis monoclonal targets Phospho-Smad1/5 (Ser463/465) (41D10) Rabbit mAb
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