X-box-binding protein 1 is required for pancreatic development in

Abstract

X-box-binding protein 1 (XBP1) is a protein containing the basic leucine zipper structure. It belongs to the cAMP-response element binding protein (CREB)/activating transcription factor transcription factor family. As the main transcription factor, spliced XBP1 (XBP1s) participates in many physiological and pathological processes and plays an important role in embryonic development. Previous studies showed that XBP1-knockout mice died because of pancreatic exocrine function deficiency, indicating that XBP1 plays an important role in pancreatic development. However, the exact role of XBP1 in pancreatic development remains unclear. This study aimed to investigate the role of XBP1 in the pancreatic development of Xenopus laevis embryos. Whole-mount in situ hybridization and quantitative real-time PCR (qRT-PCR) results revealed that the expression levels of pancreatic progenitor marker genes pdx1, p48, ngn3, and sox9 were downregulated in XBP1s morpholino oligonucleotide (MO)-injected embryos. The expression levels of pancreatic exocrine and endocrine marker genes insulin and amylase were also downregulated. Through the overexpression of XBP1s, the phenotype and gene expressions were opposite to those in XBP1s MO-injected embryos. Luciferase and chromatin immunoprecipitation assays showed that XBP1s could bind to the XBP1-binding site in the foxa2 promoter. These results revealed that XBP1 is required in the pancreatic development of Xenopus laevis and might function by regulating foxa2.

Xbp1 and Brachyury establish an evolutionarily conserved subcircuit of the notochord gene regulatory network

“…In Xenopus , morpholino-mediated knockdown of Xbp1 causes the formation of a smaller than normal notochord ( Tanegashima et al, 2009 ). Xenopus Xbp1 regulates expression of the chaperone proteins Hsp5A/Bip, DNAJ9B, and HSP90B1 ( Tanegashima et al, 2009 ), forms a regulatory loop with BMP-4 in the control of mesoderm and neural differentiation ( Zhao et al, 2003 ; Cao et al, 2006 ), and is required for pancreas development ( Yang et al, 2020 ). The present study has determined that the regulation of BMP-4 by Xbp1 is present in the Ciona notochord as well and has identified, among others, the chaperone protein DnaJc7 as a notochord target of Cr-Xbp1.…”