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Simulated-Microgravity Induced Changes in Gene Expression in Zebrafish Embryos Suggest that the Primary Cilium is Involved in Gravity Transduction.  S.J. Moorman and N. Shimada Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Piscataway, NJ

   Gravity has been a constant physical factor during the evolution and development of life on Earth.  We have been studying effects of simulated-microgravity on gene expression in transgenic zebrafish embryos expressing gfp under the influence of gene-specific promoters.  We have looked at a number of different genes expressed in a variety of different organ systems.  For instance, we have looked at beta-actin expression in the heart, eye, notochord and rohon beard neurons, hsp70 expression in the lens, alpha-A1 and beta-B1 crystallin expression in the lens, and fli1 expression in the heart and blood vessels.  Different organs and cell types show periods of maximum susceptibility during developmental periods that coincide with specific developmental events.  The organ-specific developmental events correlate with periods when primary cilia are playing organ-specific developmental roles.  In the notochord, each primary cilium is positioned to function as a ‘strain gauge’ to monitor the stresses associated with bending of the notochord in response to forces such as gravity.  Unloading the notochord by placing the embryos in a simulated-microgravity environment causes more dramatic changes in gene expression than those seen in any other tissue.  The developing cardiovascular system looses its susceptibility to simulated-microgravity induced changes in gene expression as the primary cilium of the endothelial cell becomes a flow sensor in the lumen of the blood vessels.  Rohon beard neurons show simulated-microgravity induced changes in the variability of gene expression levels that can be explained by a change in the balance between the canonical and non-canonical Wnt pathways, pathways that are influenced by the primary cilium.  The ubiquitous nature of the primary cilium as a cell organelle suggests that gravity sensing might be a general feature of all vertebrate cells where the primary cilium has not been co-opted for another sensory function.  Supported by NASA NAG2-1591