CSB Seminar Series – Felix Gunawan – University of Münster

TITLE: Endocardial tissue patterning and morphogenesis in zebrafish at single-cell resolution

Dr. Felix Gunawan
Research Group Leader
Cells-in-Motion Interfaculty Center and Faculty of Medicine,
University of Münster

Cardiac function in pumping blood throughout the body is critical for viability. The first layers that form the heart are the contractile myocardium, and the endocardium, a unique endothelial population in the heart. Although necessary for heart formation, development of the endocardium is poorly understood compared to the myocardium. Using zebrafish as a model system, my research focuses on the cellular and molecular processes driving endocardial morphogenesis and plasticity.

We first elucidated the formation of endocardial-derived heart valves that prevent retrograde blood flow. We show that heart valves form through complex morphogenetic events of specialized endocardial cells: initial collective migration, deadhesion and differentiation into fibroblastic interstitial cells, and secretion of valve matrix. These morphogenetic events are driven by distinct mechanisms: Integrinα5β1-based focal adhesions promote collective migration leading to formation of a pre-valve structure, calcium-responsive NFAT transcription factor drives endocardial cell differentiation into interstitial cells, and secretion of an elastic extracellular matrix coincides with valve tissue elongation. We are investigating the mechanisms that differentiate the specialized endocardial cells and form the elongated valve, with a particular focus on the matrisome.

We further uncovered the contribution of the endocardium into the hematopoietic system. We found stable attachment of hematopoietic cells, particularly hematopoietic stem cells and erythrocytes, to the endocardium of the beating heart. Photoconversion tracing reveals that they derive from the endocardium as well as the aorta, which is the first site of hematopoietic stem cell formation. Endocardial-derived hematopoietic cells also enter circulation and are lodged in other hematopoietic niches where blood cells proliferate. Thus, the endocardium is a de novo source of hematopoiesis and a niche to which hematopoietic cells attach. We are investigating novel regulators, which were uncovered through transcriptomic analysis of the endocardium, and the physiological functions of endocardial-to-hematopoietic transition.

Elucidating the patterning, shaping and plasticity of the endocardium is critical in understanding cardiac and hematopoietic development, with strong translational potential in therapeutic interventions of congenital heart diseases.

HOST: Dorothea Godt

LOCATION: Earth Sciences Centre, Room 1050 / Virtual

Zoom ID and passcode:

https://utoronto.zoom.us/j/87447422547

Meeting ID: 874 4742 2547

Passcode: 050579