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

Abstract

The Ventx family is one of the subfamilies of the ANTP (antennapedia) superfamily and belongs to the NK-like (NKL) subclass. Ventx is a homeobox transcription factor and has a DNA-interacting domain that is evolutionarily conserved throughout vertebrates. It has been extensively studied in Xenopus, zebrafish, and humans. The Ventx family contains transcriptional repressors widely involved in embryonic development and tumorigenesis in vertebrates. Several studies have documented that the Ventx family inhibited dorsal mesodermal formation, neural induction, and head formation in Xenopus and zebrafish. Moreover, Ventx2.2 showed functional similarities to Nanog and Barx1, leading to pluripotency and neural-crest migration in vertebrates. Among them, Ventx protein is an orthologue of the Ventx family in humans. Studies have demonstrated that human Ventx was strongly associated with myeloid-cell differentiation and acute myeloid leukemia. The therapeutic potential of Ventx family inhibition in combating cancer progression in humans is discussed. Additionally, we briefly discuss genome evolution, gene duplication, pseudo-allotetraploidy, and the homeobox family in Xenopus.

Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

“…Regulation by the homeodomain transcription factor, VENTX, was the most significantly enriched gene set for IOP genes, which has not yet been associated with glaucoma. VENTX is proposed to play important roles during embryonic patterning (by homology), including in neural crest development 50 , as well as hematopoiesis, leukemogenesis, cellular senescence and macrophage differentiation 51 . Its strongest expression in our single cell data was in lymphocytes in the anterior segment, and macrophages in the optic nerve head, proposing a novel link between immune-related processes and IOP levels.…”

The homeodomain transcription factor Ventx2 regulates respiratory progenitor cell number and differentiation timing duringXenopuslung development

“…In mice, Nkx2-1 is first detectable in the ventral foregut around the 17 somite stage at embryonic day E9.25 (Havrilak & Shannon 2017) while Sftp-c onset occurs approximately a day later at E10-10.5 (Wert et al 1993; Ikonomou et al 2017). While rodents have lost the ventx gene family during evolution (Kumar et al 2022), it is an intriguing possibility that a conserved BMP-dependent mechanism still controls timing of respiratory epithelial differentiation in vertebrates, perhaps ensuring progenitor number and gene expression programs of foregut endoderm cells are compatible with subsequent T-E morphogenesis. Indeed, in mice BMP is known to act prior to Wnt/B-catenin to suppress Sox2 expression in the ventral foregut to promote respiratory fate induction and proper levels of both BMP and Wnt signals are necessary for T-E separation (Domyan et al 2011; Woo et al 2011; Billmyre et al 2015).…”

“…The NKL subclass of HD transcription factors (TFs) are named after Kim and Nirenberg who identified several when searching for homeobox genes in Drosophila (Kim and Nirenberg 1989). In Xenopus, the ventx family has 6 members (reviewed in Kumar et al 2022); the genes ventx2 . 1 and ventx2 .…”

“…Recent work has also shown Ventx2 plays a key role in maintaining the multipotency of embryonic progenitor cells in the early blastula embryo (Scerbo et al 2012; Scerbo et al 2017) as well as maintaining the multipotency of developing neural crest cells during subsequent development (Scerbo et al 2020; Buitrago-Delgado et al 2015). The early function of Ventx2 in the blastula embryo has been suggested to be equivalent to the role mammalian Nanog plays in maintaining pluripotency of human and mouse embryonic stem cells (Scerbo et al 2012; reviewed in Kumar et al 2022).…”

“…The NKL subclass of HD transcription factors (TFs) are named after Kim and Nirenberg who identified several when searching for homeobox genes in Drosophila (Kim and Nirenberg 1989). In Xenopus, the ventx family has 6 members (reviewed in Kumar et al 2022); the genes ventx2.1 and ventx2.2 have been extensively studied during blastula and gastrula stages where they are co-expressed as part of the BMP syn-expression group (Karaulanov et al 2004;von Bubnoff et al 2005;Paulsen et al 2011) and are also regulated by Wnt/B-catenin signaling (Hikasa et al 2010). Ventx2 proteins generally act as transcriptional repressors, functioning to promote ventral mesendoderm fates and antagonize the Spemann Organizer dorsal-anterior gene regulatory network in the early Xenopus embryo (Sander et al 2007;Rankin et al 2011;Rankin and Zorn 2022).…”