Re-evaluating the functional landscape of the cardiovascular system during development

Abstract

The cardiovascular system facilitates body-wide distribution of oxygen, a vital process for the development and survival of virtually all vertebrates. However, the zebrafish, a vertebrate model organism, appears to form organs and survive mid-larval periods without a functional cardiovascular system. Despite such dispensability, it is the first organ to develop. Such enigma prompted us to hypothesize other cardiovascular functions that are important for developmental and/or physiological processes. Hence, systematic cellular ablations and functional perturbations were performed on the zebrafish cardiovascular system to gain comprehensive and body-wide understanding of such functions and to elucidate the underlying mechanisms. This approach identifies a set of organ-specific genes, each implicated for important functions. The study also unveils distinct cardiovascular mechanisms, each differentially regulating their expressions in organ-specific and oxygen-independent manners. Such mechanisms are mediated by organ-vessel interactions, circulation-dependent signals, and circulation-independent beating-heart-derived signals. A comprehensive and body-wide functional landscape of the cardiovascular system reported herein may provide clues as to why it is the first organ to develop. Furthermore, these data could serve as a resource for the study of organ development and function.