Journal article

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

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

Developmental Cell | CELL PRESS | Published : 2019

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 com..

View full abstract

Grants

Awarded by Australian Research Council


Funding Acknowledgements

This work was supported in part by an Australian Research Council Discovery grant (DP150103110 to B.M.H. and N.L.H.) and a National Health and Medical Research Council grant (1146352 to N.L.H. and B.M.H.) B.M.H. was supported by a National Heart Foundation/NHMRC Career Development Fellowship (1083811). A.K.L. was supported by a UQ Postdoctoral Fellowship. We thank Kylie Georgas for help with figures. Imaging was performed in the Australian Cancer Research Foundation's Cancer Ultrastructure and Function Facility at the Institute for Molecular Bioscience (IMB). RNA and WG sequencing were performed by the IMB sequencing facility.