In vivo cell biology in zebrafish – providing insights into vertebrate development and disease

Abstract

Over the past decades, studies using zebrafish have significantly advanced our understanding of the cellular basis for development and human diseases. Zebrafish have rapidly developing transparent embryos that allow comprehensive imaging of embryogenesis combined with powerful genetic approaches. However, forward genetic screens in zebrafish have generated unanticipated findings that are mirrored by human genetic studies: disruption of genes implicated in basic cellular processes, such as protein secretion or cytoskeletal dynamics, causes discrete developmental or disease phenotypes. This is surprising because many processes that were assumed to be fundamental to the function and survival of all cell types appear instead to be regulated by cell-specific mechanisms. Such discoveries are facilitated by experiments in whole animals, where zebrafish provides an ideal model for visualization and manipulation of organelles and cellular processes in a live vertebrate. Here, we review well-characterized mutants and newly developed tools that underscore this notion. We focus on the secretory pathway and microtubule-based trafficking as illustrative examples of how studying cell biology in vivo using zebrafish has broadened our understanding of the role fundamental cellular processes play in embryogenesis and disease.

Animal model of Sar1b deficiency presents lipid absorption deficits similar to Anderson disease

“…Obesity and other metabolic diseases such as atherosclerosis present formidable challenges to functionally dissect underlying molecular mechanisms because of small contributions of common and rare genetic variants, which do not grant sufficient quantitative power to explain the disease phenotype. Zebrafish models offer a unique experimentally amenable system to advance understanding of rare genetic diseases and metabolic disorders [35]. Zebrafish genetic models can be used to perform chemical biology screens to discover novel compounds that may be used not just to treat ANDD but other disorders of cholesterol synthesis and homeostasis.…”

Trafficking mechanisms of extracellular matrix macromolecules: Insights from vertebrate development and human diseases

“…The zebrafish crusher and two CLSD mutations affect approximately the same region of the Sec23A protein and result in remarkably similar phenotypes. This highlights the high degree of conservation of COPII-mediated collagen transport and establishes zebrafish as a strong in vivo system to model human mutations (Vacaru et al, 2013). …”

Zebrafish as Toxicological model for screening and recapitulate human diseases

“…Zebrafish heart rate and action potential are analogous to those of humans [30,31] ; also it presents highlighted genetics and regulatory networks similarities driving cell fate parallel those of higher vertebrates [31][32][33] . Moreover, cardiac performance in adult zebrafish can be detected by new noninvasive methods.…”