In spite of recent medical advancements, heart disease remains a leading cause of death worldwide. Some congenital cardiac malformations can result from heart looping defects. The heart looping is a crucial process for ensuring that the future heart chambers are aligned properly to ensure the correct function of the heart. The zebrafish has become a favored vertebrate model for studying cardiac development and disease. However, there is a lack of standardised methodology to quantitatively characterize the heart looping. One aim of this study is to provide a standardized method to quantify the heart looping degree using the zebrafish model. My method relies on access to a light sheet microscope, and 3D analysis software, and it provides various parameters to quantify the heart looping. W...[ Read more ]

In spite of recent medical advancements, heart disease remains a leading cause of death worldwide. Some congenital cardiac malformations can result from heart looping defects. The heart looping is a crucial process for ensuring that the future heart chambers are aligned properly to ensure the correct function of the heart. The zebrafish has become a favored vertebrate model for studying cardiac development and disease. However, there is a lack of standardised methodology to quantitatively characterize the heart looping. One aim of this study is to provide a standardized method to quantify the heart looping degree using the zebrafish model. My method relies on access to a light sheet microscope, and 3D analysis software, and it provides various parameters to quantify the heart looping. With this approach, I can compare these parameters on any heart phenotypes.

Furthermore, while the requirement for Ca²⁺ during normal heart function is well known, more recent evidence suggests that Ca²⁺ might also play a key role in heart morphogenesis. Thus, having a better understanding of the role of Ca²⁺ signaling in normal heart development might help identify novel therapies for acquired heart diseases, and indicate possible therapeutic options for pharmacological/genetic intervention to promote heart repair and regeneration. My data show that the introduction of the Ca²⁺ chelator, BAPTA-4K, or the treatment of zebrafish with various Ca²⁺ channel inhibitors during the heart tube formation and the heart looping affect the looping process with the observation of abnormal heart phenotypes, including misalignments of the ventricle and atrium, a decrease in the volume of the heart chambers, and failure in heart looping. My results suggest that Ca²⁺ signaling, potentially through the IP₃Rs actions, might be important for heart looping and the generation of the heart chamber volume, and thus the overall morphology of the heart.