Differential regulation of betacellulin and heparin-binding EGF-like growth factor in cultured zebrafish ovarian follicle cells by EGF family ligands

Recently the roles of epidermal growth factor (EGF) family ligands in vertebrate ovaries have received increasing attention, including betacellulin (BTC), amphiregulin (AR), heparin-binding EGF-like growth factor (HB-EGF), transforming growth factor α (TGFα), epiregulin, and EGF itself. In the zebrafish (Danio rerio), four members of EGF family have been identified by either molecular cloning or genome sequencing, which are EGF, TGFα, BTC, and HB-EGF. Although they are mostly expressed in the oocytes in the ovary, the present study demonstrated the expression of all the four EGF family ligands (egf, btc, tgfa, and hbegf) in cultured zebrafish follicle cells albeit at very low levels. Treatment of the cultured follicle cells with EGF, BTC, and HB-EGF demonstrated differential effects of these ligands on the expression of themselves. While the expression of egf was rather non-responsive to EGF, BTC, and HB-EGF, the expression of btc was consistently down-regulated by all the three molecules. In contrast, hbegf increased its expression in response to these molecules. These results suggest that there is an EGF signaling network in the zebrafish ovarian follicle, and the functionality of this network is self-regulated by its own members.