IRE1α is essential for Xenopus pancreas development

Abstract

Inositol requiring enzyme-1 (IRE1) is highly conserved from yeasts to humans. Upon the endoplasmic reticulum (ER) stress, IRE1 activates X-box-binding protein 1 (XBP1) by unconventionally splicing XBP1 mRNA, which activates the unfolded protein response (UPR) to restore ER homeostasis. In mice, IRE1α inactivity leads to embryonic death and IRE1α plays an essential role in extraembryonic tissues and the placenta. However, its precise action in the embryo proper is still unknown. In this study, the loss of function analysis was performed to investigate the function of Xenopus IRE1α (xIRE1α) during pancreas development. Firstly, the complete open reading frame of xIRE1α was amplified and the expression pattern was detected. The effects of Xenopus IRE1α and XBP1 during embryo development were detected with whole-mount in situ hybridization. The results demonstrated that xIRE1α was much closer to human IRE1α when compared with their sequence alignment. xIRE1α was expressed strongly in developing pancreas and the knockdown of xIRE1α inhibited the differentiation and specification of the pancreas. xIRE1α, which was required for cytoplasmic splicing of XBP1 pre-mRNA and XBP1MO, also showed inhibitory effects on pancreas development. These results suggest that xIRE1α is essential for pancreas development during embryogenesis and functions via the XBP1 dependent pathway.