Notch signalling in ventricular chamber development and cardiomyopathy

作者：D' Amato Gaetano; Luxan Guillermo; Luis de la Pompa Jose

来源：FEBS Journal, 2016, 283(23): 4223-4237.

DOI：10.1111/febs.13773

<jats:p>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 <jats:styled-content style="fixed-case">NOTCH</jats:styled-content> signalling may lead to disease in the form of cardiomyopathies, such as left ventricular noncompaction (<jats:styled-content style="fixed-case">LVNC</jats:styled-content>). 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 <jats:italic><jats:styled-content style="fixed-case">MIB</jats:styled-content>1</jats:italic>‐related familial <jats:styled-content style="fixed-case">LVNC</jats:styled-content> and favour the hypothesis that this cardiomyopathy has a congenital nature.</jats:p>

• 出版日期2016-12