The Xvent-2 homeobox gene is part of the BMP-4 signalling pathway controling dorsoventral patterning of Xenopus mesoderm

Abstract

We describe a novel Xenopus homeobox gene, Xvent-2, which together with the previously identified homeobox gene Xvent-1, defines a novel class of homeobox genes. vent genes are related by sequence homology, expression pattern and gain-of-function phenotype. Evidence is presented for a role of Xvent-2 in the BMP-4 pathway involved in dorsoventral patterning of mesoderm. (1) Xvent-2 is expressed in regions that also express BMP-4. (2) Xvent-2 and BMP-4 interact in a positive feedback loop. (3) Xvent-2 ventralizes dorsal mesoderm in a dose-dependent manner resulting in phenoytpes ranging from microcephaly to Bauchstuck pieces, as does BMP-4. (4) Like BMP-4 and gsc, Xvent-2 and gsc are able to interact in a crossregulatory loop to suppress each other. (5) Microinjection of Xvent-2 mRNA can rescue dorsalization by a dominant-negative BMP-4 receptor. The results suggest that Xvent-2 functions in the BMP-4 signalling pathway that antagonizes the Spemann organizer.

Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression

“…In the Ventx family, the transactivation domain (TAD) of Ventx2.2 transactivated the Ventx genes, including ventx1.1 and ventx1.2 , in a LEF1/TCF-dependent manner in Xenopus [ 14 , 22 , 24 , 87 ]. The ectopic expression of Ventx2.2 inhibited β-cat levels, causing the induction of gsk3β mRNA, leading to embryonic ventralization in Xenopus [ 105 ].…”

“…The expression of Ventx2.1 is primarily reported during blastulation after the mid-blastula transition (MBT) and leads to the development of the ventral mesodermal and ectodermal regions of Xenopus embryos. Studies have reported that BMP4/Smad1 directly induced the expression of ventx2.1 in VMZ and ectoderm in Xenopus laevis [ 24 , 82 ]. The TAD of Ventx2.1 activates the transcription of ventral and ectodermal specifiers, namely, ventx1.1 , bmp4 , and itself, in a positive feedback loop during the embryonic development of Xenopus embryos [ 14 , 24 , 25 ].…”

“…Studies have reported that BMP4/Smad1 directly induced the expression of ventx2.1 in VMZ and ectoderm in Xenopus laevis [ 24 , 82 ]. The TAD of Ventx2.1 activates the transcription of ventral and ectodermal specifiers, namely, ventx1.1 , bmp4 , and itself, in a positive feedback loop during the embryonic development of Xenopus embryos [ 14 , 24 , 25 ]. Additionally, Ventx2.1 directly binds to the 5′-upstream regions of bmp4 and ventx1.1 and activates their transcription in embryos’ gastrulae, leading to embryonic ventralization.…”

“…Studies have reported that a morpholino-based knockdown of ventx2.1 caused a partial secondary axis and expanded the Spemann-organizer region in Xenopus embryos [ 24 , 47 , 83 ]. The knockdown of ventx2.1 in the VMZ region induced the expression of Spemann-organizer specifiers, including noggin , chordin , and gsc , in Xenopus embryos.…”

“…BMP4/Smad1 is involved in a signaling path leading to the positive regulation of the expression of Vega family genes (a homolog of Ventx family in Xenopus ) in zebrafish [ 19 , 20 , 21 ]. Smad1 and Xenopus brachyury (Xbra) physically interact within the 5′-upstream regions of ventx1.1 and ventx2.1 , either in combination or separately, to augment ventx1.1 and ventx2.1 transcription in Xenopus [ 13 , 14 , 16 , 22 , 23 , 24 , 25 , 26 ]. In addition, Ventx2.2 is an ortholog of Nanog in Xenopus and exhibited a sequential and functional similarity to Nanog and Barx1 [ 27 , 28 ].…”