Abstract
ABSTRACTThe 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.
Highlights
The cardiovascular system has evolved to facilitate oxygen transport throughout the body (Aaronson et al, 2014; Gabella, 1995)
The state of hypoxia in ‘heartless’ larva was characterized by the expression levels of pan-hypoxia indicators, phd3 (Manchenkov et al, 2015; Santhakumar et al, 2012), igfbp1a (Kajimura et al, 2005) and vegfaa (Wu et al, 2015), which were previously used with zebrafish (Fig. 1C)
It has been assumed that the cardiovascular system in zebrafish is dispensable for oxygen homeostasis at least during early- to midlarval periods
Summary
The cardiovascular system has evolved to facilitate oxygen transport throughout the body (Aaronson et al, 2014; Gabella, 1995). Availability of oxygen is required for the development and function of virtually all organs. Oxygen deficiency, referred to as hypoxia, results in developmental and functional failure and/or damage of organs (Semenza, 2011, 2014; Simon and Keith, 2008). The cardiovascular system is the first functional organ to develop. Received 28 September 2017; Accepted 2 October 2017
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