Xenopus X-box binding protein 1, a leucine zipper transcription factor, is involved in the BMP signaling pathway

Abstract

We describe a novel basic leucine zipper transcription factor, XXBP-1, which interacts with BMP-4 in a positive feedback loop. It is a maternal factor and is zygotically expressed in the dorsal blastopore lip and ventral ectoderm with the exception of the prospective neural plate during gastrulation. Overexpression of XXBP-1 leads to ventralization of early embryos as described for BMP-4, and inhibits neuralization of dissociated ectoderm. Consistent with mediating BMP signaling, we show that the ectopic expression of XXBP-1 recovers the expression of epidermal keratin and reverses the dorsalization imposed by truncated BMP receptor type I, indicating that it may act downstream of the BMP receptor. Its effects can be partially mimicked by a fusion construct containing the VP16 activator domain and the XXBP-1 DNA-binding domain. In contrast, fusing the DNA-binding domain to the even-skipped repressor domain leads to upregulation of the neural markers NCAM and nrp-1 in animal cap assay. Taken together, the results suggest a role for XXBP-1 in the control of neural differentiation, possibly as an activator.

Heat Shock 70-kDa Protein 5 (Hspa5) Is Essential for Pronephros Formation by Mediating Retinoic Acid Signaling

“…1Q), and in the cement gland, pronephros (red arrow), and epidermis at tail bud stages (Fig. 1, R and S) (25). Our observations suggest that both hspa5 and xbp1 are as closely associated in embryonic development as they are in the ER stress response (39).…”

“…1, N and O). The spatial expression pattern of hspa5 was reminiscent of xbp1 (25), another key regulator of the unfolded protein response. A comparison of the expression pattern of xbp1 with that of hspa5 showed that xbp1 was co-expressed in the ventral ectoderm and dorsal blastopore lip (red arrow) during gastrulation ( Fig.…”

“…For overexpression, mRNAs were synthesized in vitro with the mMessage mMachine SP6 kit (AM 1340, Ambion). Microinjection was performed as published previously (25).…”

“…Xbp1 in turn functions in regulation of biogenesis to recover homeostasis in the ER. It is notable that a number of key components including Xbp1 and Ire1␤ are highly expressed during embryonic development; however, their functional roles during embryogenesis are not well defined (25)(26)(27). In mammalian cells, Hspa5 is predominantly localized to the ER lumen and considered a chaperone, but recent reports indicate that it is also distributed at the cell membrane and participates in signal transduction (28 -30).…”

Endoplasmic reticulum stress induced by tunicamycin disables germ layer formation in Xenopus laevis embryos

“…Since CHOP promotes apoptosis mediated by ER stress, the dramatic increase in its expression explains the death of embryos treated with different doses of TM. XBP1 is not only a key regulator in the unfolded protein response by promoting the synthesis of molecular chaperones required for ER (Lee et al, 2003) and by increasing the volume of ER (Sriburi et al, 2004;Ron and Hampton, 2004); it is also required for mesoderm specification in Xenopus (Zhao et al, 2003;Cao et al, 2006a). Unspliced XBP1 mRNA encodes a protein that is functionally inactive.…”