Thyroid hormone-upregulated hedgehog interacting protein is involved in larval-to-adult intestinal remodeling by regulating sonic hedgehog signaling pathway in Xenopus laevis

摘要

Sonic hedgehog (Shh) was previously shown to be involved in the larval-to-adult remodeling of the Xenopus laevis intestine. While Shh is transcriptionally regulated by thyroid hormone (TH), the post-transcriptional regulation of Shh signaling during intestinal remodeling is largely unknown. In the present study, we focused on a role of the pan-hedgehog inhibitor, hedgehog interacting protein (Hip), in the spatio-temporal regulation of Shh signaling. Using real-time RT-PCR and in situ hybridization, we show that Hip expression is transiently upregulated during both natural and TH-induced metamorphosis and that Hip mRNA is localized in the connective tissue adjacent to the adult epithelial primordia expressing Shh. Interestingly, the expression of bone morphogenetic protein (BMP)-4, a Shh target gene, is hardly detectable where Hip is strongly expressed. Finally, we demonstrate that Hip binds to the N-terminal fragment of processed Shh in vivo, suggesting that Hip suppresses Shh signaling through sequestering Shh.