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Start Over Author "Capon, Samuel J." Topic map kinase signaling system
2 results on '"Capon, Samuel J."'

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

Author

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, and Hogan BM

Subjects
Alternative Splicing, Animals, Cell Differentiation, Cell Lineage, Endothelial Cells cytology, Endothelial Cells metabolism, Female, Homeodomain Proteins metabolism, Humans, Lymphangiogenesis, Lymphatic Vessels cytology, Male, Neuro-Oncological Ventral Antigen, Tumor Suppressor Proteins metabolism, Veins cytology, Veins metabolism, Zebrafish, Lymphatic Vessels metabolism, MAP Kinase Signaling System, Nerve Tissue Proteins metabolism, RNA-Binding Proteins metabolism
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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
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2. The alternative splicing regulator nova2 constrains vascular erk signaling to limit specification of the lymphatic lineage

Author

Sungmin Baek, Genevieve A. Secker, Katarzyna Koltowska, Anne K. Lagendijk, Scott Paterson, Natasha L. Harvey, Kelly A. Smith, Neil I. Bower, Samuel J. Capon, Drew L. Sutton, Kazuhide S. Okuda, Cas Simons, George E.O. Muscat, Tae Gyu Oh, Gregory J. Baillie, Benjamin M. Hogan, John Toubia, Baek, Sungmin, Oh, Tae Gyu, Secker, Genevieve, Sutton, Drew L, Okuda, Kazuhide S, Paterson, Scott, Bower, Neil I, Toubia, John, Koltowska, Katarzyna, Capon, Samuel J, Baillie, Gregory J, Simons, Cas, Muscat, George EO, Lagendijk, Anne K, Smith, Kelly A, Harvey, Natasha L, and Hogan, Benjamin M

Subjects
Male, RNA splicing, MAP Kinase Signaling System, Cellular differentiation, Nerve Tissue Proteins, Cell fate determination, General Biochemistry, Genetics and Molecular Biology, Veins, Nova2, 03 medical and health sciences, 0302 clinical medicine, vascular, Neuro-Oncological Ventral Antigen, Prox1, Animals, Humans, Cell Lineage, Lymphangiogenesis, Molecular Biology, Zebrafish, 030304 developmental biology, Lymphatic Vessels, Homeodomain Proteins, 0303 health sciences, biology, Tumor Suppressor Proteins, Alternative splicing, Endothelial Cells, RNA-Binding Proteins, Cell Differentiation, Cell Biology, biology.organism_classification, Cell biology, Endothelial stem cell, lymphangiogenesis, Alternative Splicing, Lymphatic system, lymphatics, Female, signaling, 030217 neurology & neurosurgery, Developmental Biology
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. Lymphatics arise from progenitor cells that are specified along embryonic cardinal veins. How progenitor number is limited remains unknown. In this issue of Developmental Cell, Baek et al. show that Nova2 regulates a splicing program to limit vascular Flt4/Mapk/Erk signaling upstream of the master regulator of lymphatic fate, Prox1. Refereed/Peer-reviewed

Published
2019

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