Notch signalling in ventricular chamber development and cardiomyopathy.
The vertebrate heart is the first organ to form and function during embryogenesis. Primitive streak-derived cardiac progenitors located bilaterally move rostral to form the primitive heart tube that subsequently undergoes rightward looping, remodelling and septation to give rise to the mature four-chambered heart. Tightly regulated tissue interactions orchestrate the patterning, proliferation and differentiation processes that give rise to the adult ventricles. Studies in animal models have demonstrated the crucial function of the Notch signalling pathway in ventricular development and how alterations in human NOTCH signalling may lead to disease in the form of cardiomyopathies, such as left ventricular noncompaction (LVNC). In this review, we discuss how during trabecular formation and ventricular compaction, Dll4-Notch1 signals from chamber endocardium to regulate cardiomyocyte proliferation and differentiation in a noncell autonomous fashion and how, at later stages, myocardial Jag1 and Jag2 activate Notch1 in chamber endocardium to sustain chamber patterning and compaction with simultaneous coronary vessel development mediated by Dll4-Notch1. We suggest that alterations in these molecular mechanisms underlie MIB1-related familial LVNC and favour the hypothesis that this cardiomyopathy has a congenital nature.
Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Gaetano
G
D'Amato
Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Guillermo
G
Luxán
Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
José Luis
JL
de la Pompa
D000818:Animals; D009202:Cardiomyopathies / Q000196:embryology / Q000378:metabolism*; D004699:Endocardium / Q000196:embryology / Q000378:metabolism; D006352:Heart Ventricles / Q000196:embryology / Q000378:metabolism; D006801:Humans; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D038081:Organogenesis; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
D051880:Receptors, Notch

NOTCH
; cardiomyopathy; compaction; heart; left ventricular noncompaction; signalling; trabeculae; ventricles