The heart is the first functional organ formed in mammalian embryonic development. Organ morphogenesis depends on the spatiotemporal arrangement of cells during development. The most well-known mechanism that contributes to the final shape of an organ is cellular intercalation in response to morphogens. A less well-known but essential mechanism is oriented cell division (OCD). OCD is typically determined by evaluating the alignment of the mitotic spindles relative to organ and anatomical axes. OCD is a potential asymmetric cell division that contributes to cellular diversity, differentiation and organogenesis during development. A third and novel mechanism is cellular elongation-mediated cellular orientation, which has not been previously studied during organ morphogenesis. We unravels a novel phenomenon that cardiomyocytes display spatiotemporal cellular orientation during ventricular wall morphogenesis, and its disruption causes a round shape to the cardiomyocytes, which leads to abnormal trabecular and ventricular wall morphogenesis. Furthermore, we established a novel mechanism by which Numb modulates cellular shape and orientation, and consequently trabecular and ventricular wall morphogenesis by regulating N-Cadherin recycling to the plasma membrane.
In conclusion, during ventricular wall morphogenesis, the cardiomyocytes display spatiotemporal cellular orientation and organization, and their disruption leads to abnormal trabecular and ventricular wall morphogenesis. Numb modulates cellular orientation and organization, and consequent trabecular and ventricular wall morphogenesis by regulating N-Cadherin recycling to plasma membrane. Our studies might reveal the basis of left-ventricular noncompaction.
Dr. Mingfu Wu currently is an associate professor at Albany Medical College, New York. He obtained his PhD at Kansas State University in 2005, and received postdoc training at Duke University from 2006 to 2007, and at UT Southwestern from 2008 to 2010. He became an independent principle investigator in 2011 at Albany Medical College. He has been studying cell polarity and asymmetric cell division using different models, including C. elegans, mouse hematopoietic stem cell, epicardial cells and cardiac progenitor cells. His lab focuses on the mechanism of trabecular formation and compaction and the multipotency and heterogeneity of epicardial cells during development and regeneration. His lab has published multiple papers and significantly contributes to the understanding of trabecular formation. He has been invited to present the topic of trabecular formation in the major conferences such as AHA and BCVS organized by AHA.