Functional Modulation of Cardiac Form through Regionally Confined Cell Shape Changes

Abstract

Developing organs acquire a specific three-dimensional form that ensures their normal function. Cardiac function, for example, depends upon properly shaped chambers that emerge from a primitive heart tube. The cellular mechanisms that control chamber shape are not yet understood. Here, we demonstrate that chamber morphology develops via changes in cell morphology, and we determine key regulatory influences on this process. Focusing on the development of the ventricular chamber in zebrafish, we show that cardiomyocyte cell shape changes underlie the formation of characteristic chamber curvatures. In particular, cardiomyocyte elongation occurs within a confined area that forms the ventricular outer curvature. Because cardiac contractility and blood flow begin before chambers emerge, cardiac function has the potential to influence chamber curvature formation. Employing zebrafish mutants with functional deficiencies, we find that blood flow and contractility independently regulate cell shape changes in the emerging ventricle. Reduction of circulation limits the extent of cardiomyocyte elongation; in contrast, disruption of sarcomere formation releases limitations on cardiomyocyte dimensions. Thus, the acquisition of normal cardiomyocyte morphology requires a balance between extrinsic and intrinsic physical forces. Together, these data establish regionally confined cell shape change as a cellular mechanism for chamber emergence and as a link in the relationship between form and function during organ morphogenesis.

microRNA-138 modulates cardiac patterning during embryonic development

“…Ventricular cardiomyocytes normally become elongated by 48 hpf as they differentiate, whereas myocytes that normally persist around the AVC remain in a more rounded, immature state (24). Confocal microscopy of miR-138 mo-1 fish revealed defects in elongation of ventricular cardiomyocytes and in cardiac looping at 48 hpf ( Fig.…”

“…1 E-G). Blood flow and contractility, which are important stimuli for cardiomyocyte maturation (24), appeared grossly intact at 48 hpf (Movie S3 and Movie S4). A second 31-nt morpholino against the pri-miR-138 (mo-2) produced a similar defect, suggesting that the morpholinoinduced effects were specifically because of the down-regulation of miR-138 (Fig.…”

Calcium influx through L-type CaV1.2 Ca2+ channels regulates mandibular development

“…To confirm that the reduced mandible size observed after morpholino treatment was independent of the effect upon cardiac function, we analyzed developing mandibles in the offspring of weak atrium (wea) and half-hearted (haf) double heterozygotes (wea;haf). The wea mutants lack atrial contractility and the haf mutants lack ventricular contractility (10). Homozygous double mutants were identified at 48 hpf by a complete lack of atrial and ventricular contractility.…”

Le débit cardiaque, acteur majeur de la morphogenèse asymétrique des arcs aortiques

“…Les bases cellulaires et moléculaires de cette morphogenèse asymétrique restent inconnues. Cependant, des modèles animaux (poisson et souris) suggèrent que l'hémodynamique embryonnaire puisse être une composante déterminante dans la latéralité des organes [1][2][3][4].…”

“…Ainsi, l'anatomie définitive est asymé-trique. Les récentes recherches menées sur le rôle de l'hémodynamique au cours du développement embryonnaire ont démontré qu'il existait un lien entre le débit cardiaque et le changement de forme des cellules et/ou l'expression de gènes [1][2][3][4]. Une nouvelle publication vient renforcer cette idée en démontrant que l'asymétrie de la crosse aortique est déterminée par le débit cardiaque préférentiel dans les arcs aortiques gauches [5].…”