The zebrafish as a model organism for the study of apoptosis

Abstract

Apoptosis plays important roles in embryogenesis, tissue homeostasis, and immune system regulation. The zebrafish (Danio rerio) is a powerful vertebrate model organism that has been extensively used to study apoptotic cell death during normal development and under conditions of cellular stress. In the past 5 years, a detailed picture has begun to emerge of the molecular underpinnings of the cell-intrinsic and the cell-extrinsic apoptosis signaling pathways in zebrafish. We begin this review with an introduction to the techniques and experimental approaches that are used to study apoptosis in zebrafish. We follow with a general overview of developmental apoptosis during zebrafish embryogenesis. Finally, we present a comprehensive review of the intrinsic and extrinsic apoptosis pathways in zebrafish, focusing on the high degree of conservation with humans and other mammals. Recent publications that draw upon the unique advantages of the zebrafish system to study novel aspects of apoptosis regulation and function are highlighted throughout.

Repression of Puma by Scratch2 is required for neuronal survival during embryonic development

“…Hence, scratch2 knockdown leads to cell-autonomous activation of the intrinsic apoptotic pathway in cells that normally express scratch2, subsequently inducing cell death in adjacent cells through an extrinsic apoptotic pathway. 15 Indeed, B-cell lymphoma 2 (bcl2) overexpression completely abolished the apoptotic phenotype in 75% of embryos co-injected with scratch2 MO (n ¼ 65; Figure 7h), both in endogenous territories of scratch2 expression and in adjacent cells.…”

“…Scratch2 deficiency provokes cell-autonomous death of differentiated neurons that otherwise express scratch2. Similarly, it activates non-autonomous cell death through an extrinsic apoptotic pathway in progenitor cells that do not normally express scratch2, revealing a role for the extrinsic apoptotic pathway in the zebrafish nervous system 15 (Figure 8b). Similar cell death of both proliferative and differentiated cells occurs in the intestine of young mice deficient for Mdm2.…”

“…Therefore, we investigated the role of Scratch in vertebrate cell survival using zebrafish, a suitable model to study cell death and p53 signaling. [14][15][16] We characterized three zebrafish scratch genes that were specifically expressed in the nervous system and we found that scratch2 acts as a survival factor in neurons in vivo. We show that scratch2 is directly upregulated by p53 and that it represses puma transcription after DNA damage.…”

Control of Programmed Cell Death During Zebrafish Embryonic Development

“…This feature allows the IAPs not only to block caspase activity but also to promote their degradation by the proteasome [18]. It should be noted that six IAP proteins are found in zebrafish [19]. Zebrafish IAPs including survivins (BIRC5a and BIRC5b) appear to play a role in embryonic development.…”

“…These results highlight the extremely cautious, which has to be employed when potential actors of the apoptotic program are studied by the morpholino strategy. In addition to the use of different morpholino sequences targeted, the same gene and crucial rescue experiments, co-expression of p53 morpholino is now commonly used to discern between genespecific and off-target effects [19]. Indeed, p53 is not required for proper early embryos development and p53 morpholino does not interfere with other gene-specific phenotypes [87,88].…”