PV.1 induced by FGF-Xbra functions as a repressor of neurogenesis in Xenopus embryos

Abstract

During Xenopus early development, FGF signaling is involved in mesoderm formation and neurogenesis by modulating various signaling cascades. FGF-MAPK signaling induces Xbra expression, which maintains mesodermal fate through an autocatalytic-loop. Interestingly, previous reports have demonstrated that basic FGF (bFGF) treatment alone does not induce neurogenesis in ectodermal explants, even though FGF signaling inhibits BMP signaling via phosphorylation in Smad1 linker region. In addition, the overexpression of dominantnegative Xbra induces neurogenesis in ectodermal explants. However, the detailed mechanism underlying these phenomena has not yet been clarified. In this work, we showed that bFGF-Xbra signaling increased the PV.1 expression. DN-Xbra was found to decrease PV.1 expression, and the co-injection of PV.1 with DN-Xbra reduced neurogenesis in ectodermal explants. Furthermore, the knockdown of PV.1 induced neurogenesis in bFGF-treated ectodermal explants. Taken together, our results demonstrate that FGF-Xbra signaling induces PV.1 expression and that PV.1 functions as a neural repressor in the FGF-treated ectoderm. [BMB Reports 2014; 47(12): 673-678]

Xbra and Smad-1 response elements cooperate in PV.1 promoter to inhibit the early neurogenesis inXenopusembryos

“…Moreover, the C-terminal domain of PV.1 leads the inhibition of dorsal fate determination and neural inhibition (Hawley et al, 1995; Hwang et al, 2002; Hwang et al, 2003). Recent studies observed that FGF signaling plays a dual role to regulate the BMP-4/Smad-1 signaling (Pera et al, 2003; Yoon et al, 2014b). FGF signaling inhibits BMP-4/Smad-1 signaling through inhibiting the Smad-1 activity in an MAPK-dependent manner (Pera et al, 2003).…”

“…However, FGF alone is not sufficient to induce neurogenesis in Xenopus embryos (Pera et al, 2003). Later on, a study showed that FGF signaling positively regulates expression of PV.1 (A transcriptional factor of BMP-4 signaling) in a Xbra-dependent manner, causing to neural inhibition (Yoon et al, 2014b). The involvement of BMP-4/Smad-1 and FGF-Xbra signaling may facilitate a signaling crosstalk in the regulation of PV.1 expression during embryonic development of Xenopus.…”

“…The involvement of BMP-4/Smad-1 and FGF-Xbra signaling may facilitate a signaling crosstalk in the regulation of PV.1 expression during embryonic development of Xenopus. (Lee et al, 2011; Yoon et al, 2014b). However, the detailed molecular mechanism of BMP-4/Smad-1 and FGF/Xbra-mediated signaling crosstalk in the regulation of PV.1 transcription is largely unknown.…”

“…The proximal promoter region of PV.1 contains various cis-acting response elements for transcriptional activation of BMP-4 downstream targets, including Xvent-2, Oaz, and Smad-1 (Lee et al, 2011). Moreover, PV.1 negatively regulates expression of neurogenesis-promoting genes, including Chordin, Zic3, FoxD5b, Ngnr, and N-CAM (Melby et al, 1999; Trindade et al, 1999; Lee et al, 2002; Yoon et al, 2014b). However, the detailed molecular mechanism of PV.1-mediated inhibition of early neurogenesis is still awaited to delineate.…”

“…Recent studies have been documented that T-box transcriptional activator proteins bind to a consensus sequences (A/G)(A/T)(A/T)NTN(A/G)CAC(C/T)T within promoter region of its targeted genes, promoting to transcription activation of targeted genes (Conlon et al, 2001; Kusch et al, 2002). Our previous study addressed that FGF signaling promotes PV.1 expression, causing to neural inhibition while dominant-negative Xbra (DN-Xbra) can trigger early neurogenesis in ectoderm through inhibiting the PV.1 expression (Yoon et al, 2014b). This study suggests that FGF signaling induces the PV.1 expression in a Xbra-dependent manner.…”