Hooked on zebrafish: insights into development and cancer of endocrine tissues

Abstract

Zebrafish is emerging as a unique model organism for studying cancer genetics and biology. For several decades zebrafish have been used to study vertebrate development, where they have made important contributions to understanding the specification and differentiation programs in many tissues. Recently, zebrafish studies have led to important insights into thyroid development, and have been used to model endocrine cancer. Zebrafish possess a unique set of attributes that make them amenable to forward and reverse genetic approaches. Zebrafish embryos develop rapidly and can be used to study specific cell lineages or the effects of chemicals on pathways or tissue development. In this review, we highlight the structure and function of endocrine organs in zebrafish and outline the major achievements in modeling cancer. Our goal is to familiarize readers with the zebrafish as a genetic model system and propose opportunities for endocrine cancer research in zebrafish.

Animal models of MEN1

“…Fish do not possess a typical parathyroid gland; yet, studies from Okabe and Graham (2004) proved that the gills of fish are evolutionarily related structures that express calcium-sensing receptors and PTH. A transgenic zebrafish strain deleted for cdc73 has been suggested as a model for parathyroid tumors, as the human homologue HRPT2/CDC73 is responsible for the hyperparathyroidism-jaw tumor syndrome (Carpten et al 2002, Bourque & Houvras 2011.…”

Zebrafish as an innovative model for neuroendocrine tumors

“…Most of the players, pathways, and feedback loops of endocrine system are highly conserved from zebrafish to human (Bourque & Houvras 2011, Lohr & Hammerschmidt 2011. Orthologs for several mammalian neurohormones have been identified and localized in zebrafish (Toro et al 2009, Lohr & Hammerschmidt 2011.…”

“…Indeed, parathyroid gland and the gills of fish are evolutionarily related structures (Bourque & Houvras 2011). In humans, germline inactivation of the HRPT2/CDC73 tumor suppressor gene, coding for parafibromin and discovered in the context of the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, has been reported in 50-75% of HPT-JT cases and in about 14% of familial isolated hyperparathyroidism (Carpten et al 2002, Bricaire et al 2013).…”

“…Interestingly, the zebrafish ortholog of cdc73 has been identified in a genetic suppressor screen where it modulates erythropoiesis (Bai et al 2010), and oligodendrocyte differentiation (Kim et al 2012). The identification of a zebrafish cdc73 mutant may provide an attractive device for creating a zebrafish model of parathyroid tumors (Bourque & Houvras 2011).…”

“…Malignant transformation of C-cells by RET oncogene leads to MTC in humans, but the role of surrounding follicular thyroid cells is presently unknown. So it would be interesting to determine the disease phenotype emerging in species where C-cells are not colocalized with thyroid epithelial cells (Bourque & Houvras 2011). Indeed, thyroid epithelial cells are able to synthesize extracellular matrix components in mammals, and it has been postulated that extracellular matrix may have a role in the pathogenesis and progression of MTC (Lekmine et al 1999).…”