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The Alternative Splicing Regulator Nova2 Constrains Vascular Erk Signaling to Limit Specification of the Lymphatic Lineage.

Abstract：

: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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Baek S,Oh TG,Secker G,Sutton DL,Okuda KS,Paterson S,Bower NI,Toubia J,Koltowska K,Capon SJ,Baillie GJ,Simons C,Muscat GEO,Lagendijk AK,Smith KA,Harvey NL,Hogan BM

doi

10.1016/j.devcel.2019.03.017

subject

Has Abstract

pub_date

2019-04-22 00:00:00

pages

279-292.e5

issue

2

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(19)30228-X

journal_volume

49

pub_type

杂志文章

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