Zebrafish as a model to study autophagy and its role in skeletal development and disease
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REVIEW
Zebrafish as a model to study autophagy and its role in skeletal development and disease Joanna J. Moss1,2 · Chrissy L. Hammond2 · Jon D. Lane1 Accepted: 31 August 2020 © The Author(s) 2020
Abstract In the last twenty years, research using zebrafish as a model organism has increased immensely. With the many advantages that zebrafish offer such as high fecundity, optical transparency, ex vivo development, and genetic tractability, they are well suited to studying developmental processes and the effect of genetic mutations. More recently, zebrafish models have been used to study autophagy. This important protein degradation pathway is needed for cell and tissue homeostasis in a variety of contexts. Correspondingly, its dysregulation has been implicated in multiple diseases including skeletal disorders. In this review, we explore how zebrafish are being used to study autophagy in the context of skeletal development and disease, and the ways these areas are intersecting to help identify potential therapeutic targets for skeletal disorders. Keywords Autophagy · Zebrafish · Bone · Development · Tools
Introduction Autophagy Autophagy is a catabolic process which enables the breakdown of cytosolic components into their basic biomolecular constituents by lysosomal degradation, so that they may be recycled for further use. It is an essential process required during cell differentiation and it contributes to the maintenance of cellular homeostasis where its primary function is to mobilise nutrients to sustain vital cellular functions during stress (Dikic and Elazar 2018). Since the first mechanistic descriptions of the autophagy process in 1967 by Christian de Duve (Deter and De Duve 1967), extensive research has been carried out to understand the autophagy pathways and their molecular control. Whilst these studies have established the importance of autophagy in cell differentiation * Chrissy L. Hammond [email protected] * Jon D. Lane [email protected] 1
School of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol, UK
School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, UK
2
and survival, they have also highlighted the vast number of housekeeping roles it plays, and the how its dysregulation contributes to the pathology of multiple diseases, including common skeletal disorders such as forms of arthritis and osteoporosis (Bouderlique et al. 2016; Cadwell and Debnath 2018; Jiang and Mizushima 2014; Levine and Kroemer 2019; Ochotny et al. 2013). Autophagy can be divided into three main forms; chaperone-mediated autophagy (CMA), microautophagy and macroautophagy; each being delineated by the method of cargo delivery to the lysosome. This review will focus on macroautophagy (hereafter termed autophagy), as this considered to be the major form of autophagy and remains the most widely studied (Mizushima 2007). It involves the de novo formation of an intermediate organelle, the autophagosome, to deliver car
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