Meeting Abstract
15.11 Monday, Jan. 4 Exploring the duplicated zebrafish genes: Discovery of a novel role of insulin-like growth factor binding protein (IGFBP)-5 in calcium homeostasis DAI, W*; HWANG, PP; DUAN, C; University of Michigan; Institute of Cellular and Organismic Biology, Taiwan; University of Michigan cduan@umich.edu
Insulin-like growth factor binding proteins (IGFBPs) are high affinity binding partners for IGFs and play important roles in regulating IGF availability and actions. IGFBP-5 is the most conserved member of this gene family. Recently, we have shown that zebrafish have two distinct IGFBP-5 genes, likely resulted from a gene duplication event during teleost evolution. These two genes exhibited distinct spatial and temporal expression patterns. Interestingly, one of the two genes, igfbp-5a, is specifically expressed in epidermal ionocytes surrounding the yolk sac and gill arches. Fluorescent double-labeled in situ hybridization analysis revealed that igfbp-5a mRNA is co-localized with trpv6 mRNA but not with the H+-ATPase atp6v1al mRNA. In fish, the epithelial Ca2+ channel Trpv6-expressing ionocytes are known to be important for calcium uptake. Acclimation of zebrafish embryos to artificial water with altered ion concentrations showed that igfbp-5a mRNA levels are increased in response to reduced calcium concentrations. Low Ca2+ freshwater also increased the number and size of the igfbp-5a-mRNA expressing ionocytes, while it had no effect on the atp6v1al-mRNA expressing ionocytes. To test the role of IGFBP-5a in these cells and in calcium metabolism, antisense morpholinos were used to knockdown IGFBP-5a in zebrafish embryos. Compared with the control embryos, IGFBP-5a knocked down embryos had increased calcium content and calcium influx. Knocking down of IGFBP-5a also resulted in an increase in the number of Trpv6-expressing ionocytes. These findings suggest that IGFBP-5a is specifically expressed in Trpv6-expressing ionocytes and its expression is regulated by environmental calcium concentrations. Our study in zebrafish has also unraveled a novel role of IGFBP-5 in calcium homeostasis.
