Zebrafish Tmem230a cooperates with the Delta/Notch signaling pathway to modulate endothelial cell number in angiogenic vessels

• Published in: Journal of cellular physiology 2018-02, Vol.233 (2), p.1455-1467
• Main Authors: Carra, Silvia, Sangiorgio, Lorenzo, Pelucchi, Paride, Cermenati, Solei, Mezzelani, Alessandra, Martino, Valentina, Palizban, Mira, Albertini, Alberto, Götte, Martin, Kehler, James, Deflorian, Gianluca, Beltrame, Monica, Giordano, Antonio, Reinbold, Rolland, Cotelli, Franco, Bellipanni, Gianfranco, Zucchi, Ileana
• Format: Article
• Language: English
• Subjects: Aberration; Amino Acid Sequence; Angiogenesis; Animals; Animals, Genetically Modified; Arteries; Base Sequence; blood vessel formation growth; Blood vessels; Cell number; Cell Proliferation; Conserved Sequence; Danio rerio; Delta/Notch signaling; Drug discovery; Embryogenesis; Embryonic growth stage; Endothelial cells; Endothelial Cells - metabolism; Gene expression; Gene Expression Regulation, Developmental; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Neovascularization, Physiologic; Network formation; Notch protein; Receptors, Notch - genetics; Receptors, Notch - metabolism; Regenerative medicine; Signal Transduction; Signaling; transmembrane protein 230; Vascular endothelial growth factor; Vegf signaling; Zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26032

During embryonic development, new arteries, and veins form from preexisting vessels in response to specific angiogenic signals. Angiogenic signaling is complex since not all endothelial cells exposed to angiogenic signals respond equally. Some cells will be selected to become tip cells and acquire migration and proliferation capacity necessary for vessel growth while others, the stalk cells become trailer cells that stay connected with pre‐existing vessels and act as a linkage to new forming vessels. Additionally, stalk and tip cells have the capacity to interchange their roles. Stalk and tip cellular responses are mediated in part by the interactions of components of the Delta/Notch and Vegf signaling pathways. We have identified in zebrafish, that the transmembrane protein Tmem230a is a novel regulator of angiogenesis by its capacity to regulate the number of the endothelial cells in intersegmental vessels by co‐operating with the Delta/Notch signaling pathway. Modulation of Tmem230a expression by itself is sufficient to rescue improper number of endothelial cells induced by aberrant expression or inhibition of the activity of genes associated with the Dll4/Notch pathway in zebrafish. Therefore, Tmem230a may have a modulatory role in vessel‐network formation and growth. As the Tmem230 sequence is conserved in human, Tmem230 may represent a promising novel target for drug discovery and for disease therapy and regenerative medicine in promoting or restricting angiogenesis. We have identified in zebrafish, that the transmembrane protein Tmem230a is a novel regulator of angiogenesis by its capacity to regulate the number of the endothelial cells in intersegmental vessels by co‐operating with the Delta/Notch signaling pathway. Modulation of Tmem230a expression by itself is sufficient to rescue improper number of endothelial cells induced by aberrant expression or inhibition of the activity of genes associated with the Dll4/Notch pathway in zebrafish. As the Tmem230 sequence is conserved in human, tmem230 may represent a promising novel target for drug discovery and for disease therapy and regenerative medicine in promoting or restricting angiogenesis.