Sequential Notch activation regulates ventricular chamber development Journal Article
| Authors: | D'Amato, G.; Luxán, G.; Del Monte-Nieto, G.; Martínez-Poveda, B.; Torroja, C.; Walter, W.; Bochter, M. S.; Benedito, R.; Cole, S.; Martínez, F.; Hadjantonakis, A. K.; Uemura, A.; Jiménez-Borreguero, L. J.; De La Pompa, J. L. |
| Article Title: | Sequential Notch activation regulates ventricular chamber development |
| Abstract: | Ventricular chambers are essential for the rhythmic contraction and relaxation occurring in every heartbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is poorly understood. We show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation, and later coordinates ventricular patterning and compaction with coronary vessel development to generate the mature chamber, through a temporal sequence of ligand signalling determined by the glycosyltransferase manic fringe (MFng). Early endocardial expression of MFng promotes Dll4-Notch1 signalling, which induces trabeculation in the developing ventricle. Ventricular maturation and compaction require MFng and Dll4 downregulation in the endocardium, which allows myocardial Jag1 and Jag2 signalling to Notch1 in this tissue. Perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; nonhuman; animal cell; mouse; animal tissue; embryo; notch receptor; angiogenesis; membrane protein; down regulation; heart muscle; endocardium; heart development; notch1 receptor; jagged1; glycosyltransferase; priority journal; article; heart ventricle; coronary blood vessel; glycosyltransferase manic fringe; jagged2; trabecular meshwork |
| Journal Title: | Nature Cell Biology |
| Volume: | 18 |
| Issue: | 1 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2016-01-01 |
| Start Page: | 7 |
| End Page: | 20 |
| Language: | English |
| DOI: | 10.1038/ncb3280 |
| PROVIDER: | scopus |
| PUBMED: | 26641715 |
| PMCID: | PMC4816493 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2016 -- Source: Scopus |
