Morphogenetic control of zebrafish cardiac looping by Bmp signaling

SALIM ABDELILAH-SEYFRIED; MELINA HEISE; VERONICA LOMBARDO

Kiel

Conferencia; Joint Meeting of the German and Japanese Societies of Developmental Biologists; 2017

Cardiac looping is an essential and highly conserved process during morphogenesis of the vertebrate heart. This process positions the different regions of the developing heart tube into proximity of their correct topographical region within the adult heart. Cardiac looping involves an early C-looping, during which the ventricle bends to the right and a later S-looping, during which the atrium is shifted cranially in a leftward position next to the ventricle. A number of genetic and epigenetic factors have been implicated in cardiac looping but the exact mechanism(s) regulating this process are still unclear. In this project, we examined the morphogenetic rearrangements during S-looping of the zebrafish heart as well as their regulation by genetic and epigenetic factors. We have combined Brainbow technology with 4D live imaging to assess whether S-looping in zebrafish is morphogenetically comparable with processes that have been described in mammalia and will present the outcome of this analysis. We have also characterized the role of the Bone morphogenetic protein (Bmp) pathway in this process. High-resolution temporal-spatial analysis of S-looping revealed that myocardial cells at the boundary between ventricle and atrium acquire high columnar and anisotropic epithelial cell shapes; this causes a constriction of the atrio-ventricular canal (AVC) which facilitates the bending of the heart tube. Upon inhibition of Bmp signaling, an increased fraction of hearts failed to undergo S-looping, which correlated with more cuboidal morphologies of AVC myocardial cells. We are currently elucidating the potential interplay between Bmp signaling and the regulation of actomyosin cytoskeletal networks and will report on these findings as well.