title: Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.
abstract: Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity.
authors.affiliation: Laboratory for Organogenesis and Regeneration, GIGA- Research, University of Liège, B-4000, Liège, Sart-Tilman, Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Aceto
authors.affiliation: BasAM, Norwegian University of Life Sciences, Vetbio, 0033 Dep, Oslo, Norway.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Nourizadeh-Lillabadi
authors.affiliation: GIGA & Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium.
authors.forename: Raphael
authors.initials: R
authors.lastname: Marée
authors.affiliation: Unité de soutien méth. en Biostatistique et Epidémiologie, University of Liège, B23, Sart Tilman, Liège, Belgium.
authors.forename: Nadia
authors.initials: N
authors.lastname: Dardenne
authors.affiliation: Laboratory for Organogenesis and Regeneration, GIGA- Research, University of Liège, B-4000, Liège, Sart-Tilman, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jeanray
authors.affiliation: GIGA & Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: Wehenkel
authors.affiliation: BasAM, Norwegian University of Life Sciences, Vetbio, 0033 Dep, Oslo, Norway.
authors.forename: Peter
authors.initials: P
authors.lastname: Aleström
authors.affiliation: DESC (Dutch Experiment Support Center), Department of Oral and Maxillofacial Surgery / Oral Pathology, VU University Medical Center & Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands; ESA-ESTEC, TEC-MMG, NL-2200 AG, Noordwijk, The Netherlands.
authors.forename: Jack J W A
authors.initials: JJ
authors.lastname: van Loon
authors.affiliation: Laboratory for Organogenesis and Regeneration, GIGA- Research, University of Liège, B-4000, Liège, Sart-Tilman, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Muller
mesh_terms: D000818:Animals; D047108:Embryonic Development; D006112:Gravitation; D006728:Hormones / Q000502:physiology*; D015027:Zebrafish / Q000033:anatomy & histology* / Q000196:embryology / Q000502:physiology*
chemical_list: D006728:Hormones