Estrogen receptors and zebrafish development
Estrogens are steroid hormones that exert a variety of effects in diverse target tissues. They act on target genes mainly via the genomic pathway through binding to their nuclear receptors (estrogen receptors, ERs). In zebrafish (Danio rerio), three subtypes have been characterized, ERα, ERβ1 and ERβ2. In addition to natural ligands, xenoestrogens are able to bind to ERs, thereby activating or inactivating a number of genes leading to altered production of proteins in estrogen target cells. We investigated the role of ERs in early developmental processes in zebrafish, with particular focus on non-reproductive functions, aiming to identify new targets for xenoestrogens in embryonic development. The measurement of relative transcript abundance of the three subtypes during normogenesis and in response to certain xenoestrogens suggested that ERα might be the subtype responsible for endocrine disruption in early life stages, while ERβ2 might be the main mediator of natural actions of estrogens. The study of the localization of the three subtypes revealed the presence of ERβ2 in the head and in the neuromasts, the organs of the lateral line. The role of ERβ2 was further analyzed by morpholino knock-down of the corresponding protein synthesis. The ERβ2 morphants showed abnormal neuromast development (Fig. 1). Further investigations gave indications for a function of ERβ2 in hair cell differentiation (Fig. 2) and a cross-talk between estrogen and Notch signalling pathways (1). Neuromasts are proposed as a novel endpoint for assessing subtle effects of toxicants, linking toxicological and developmental knowledge (2).
Neuromast detection with live staining (FM1-43)
in 72 hpf larvae.
(A-C) Larvae injected with coMO at 15 μM.
(D-F) Larvae
injected with ERβ2 MO at 15μM.
Arrowheads point to neuromasts with functional
hair cells. Scale bar = 200μm.
References
1. M Froehlicher, A Liedtke, K Groh, H Lopez-Schier, SCF Neuhauss, H Segner, RIL Eggen, 2009. Estrogen receptor subtype β2 is involved in neuromast development in zebrafish (Danio rerio) larvae. Dev. Biol., 330, 32-43.
2. M Froehlicher, A Liedtke, KJ Groh, SCF Neuhauss, H Segner, RIL Eggen, in press. Zebrafish (Danio rerio) neuromast: Promising biological endpoint linking developmental and toxicological studies. Aquat. Tox. (Epub 2009 Apr 24)
Eawag News 64d, April 2008