Insulin-like growth factors (IGFs) are potent regulators of development and homeostasis. IGF-binding proteins (IGFBPs) are important modulators of IGF signaling. In this study, I took advantage of the zebrafish model to investigate the in vivo function of the IGF system, in particular IGFBP5. Two zebrafish igfbp5 genes were identified, exhibiting functional diversification both in expression patterns and biochemical properties. One of them, igfbp5a, is specifically expressed in the trpv6-expressing NaR cells in the yolk skin of zebrafish embryos and larvae. These cells mediate epithelial Ca2+ absorption from the water, and are functionally equivalent to the enterocytes in the mammalian intestinal epithelium. Morpholino knockdown of igfbp5a increased the number of the NaR cells and elevated Ca2+ content and Ca2+ influx in the embryos, suggesting that Igfbp5a functions as a regulator of Ca2+ homeostasis by negatively modulating the population of the NaR cells. In zebrafish larvae, igfbp5a and trpv6 co-expressing NaR cells increase their number dramatically in low-Ca2+ water. IGF1R downstream Akt signaling is specifically activated upon low-Ca2+ treatment. Pharmacological inhibition of IGF1R or PI3K abolished the low-Ca2+ induced cell proliferation. These findings suggest that IGF signaling is required for the increase of the NaR cells during low-Ca2+ acclimation. Taken together, this study reveals previously unknown roles of IGF and IGFBP5 in epithelial Ca2+ transport. It also provides new insight into the molecular regulation of growth factor signaling during development and physiological adaptation
To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.