Vax1is a novel homeobox-containing gene expressed in the developing anterior ventral forebrain

Abstract

The vertebrate forebrain is formed at the rostral end of the neural plate under the regulation of local and specific signals emanating from both the endomesoderm and neuroectoderm. The development of the rostral and ventral forebrain in particular was difficult to study, mainly because no specific markers are available to date. Here, we report the identification of Vax1, a novel homeobox-containing gene identified in mouse, Xenopus and human. It is closely related to members of the Not and Emx gene families, all of which are required for the formation of structures where they are expressed. In mouse and Xenopus, Vax1 expression first occurs in the rostral neural plate, in the medial anterior neural ridge and adjacent ectoderm. Later, at midgestation in the mouse and tadpole stage in Xenopus, the expression remains confined in the derivatives of this territory which differentiate into rostromedial olfactory placode, optic nerve and disc, and anterior ventral forebrain. Together, these observations suggest that Vax1 could have an early evolutionary origin and could participate in the specification and formation of the rostral and ventral forebrain in vertebrates. Comparison of the limits of the expression territory of Vax1 with that of Dlx1, Pax6 and Emx1 indicates that the corticostriatal ridge is a complex structure with distinct identifiable genetic compartments. Besides, the study of Vax1 expression in Pax6-deficient homozygous brains indicates that its regulation is independent of Pax6, although the expression patterns of these two genes appear complementary in wild-type animals. Vax1 chromosomal location is mapped at the distal end of the mouse chromosome 19, linked with that of Emx2. These two genes may have arisen by tandem duplication. The Vax1 gene is thus an interesting new tool to study the rostral ventral forebrain patterning, morphogenesis and evolution as well as the terminal differentiation of the forebrain in mouse and Xenopus.

Altered Expression of Candidate Genes in Mayer–Rokitansky–Küster–Hauser Syndrome May Influence Vaginal Keratinocytes Biology: A Focus on Protein Kinase X

“…Similarly, PRKX seemed to determine the upregulation of DMBX1, which is expressed in the urogenital system and testis [74], as well as the positive modulation of VAX1 in VK2 E6/E7 cells. VAX1 interacts with EMX2 protein [75], which was found to be indispensable for the formation of both MD and WD in mice [76]. Moreover, in our study, ectopic PRKX overexpression seemed to upregulate HOXD13, whose alteration has been linked to syndromes affecting genitourinary development [77], renal agenesis [78], and limb malformations such as synpolydactyly and polydactyly [79].…”

The risk of nonsyndromic cleft lip with or without cleft palate and Vax1 rs7078160 polymorphisms in southern Han Chinese

“…Vax1 was a crucial gene for the development of the basal forebrain and visual system in animal experiments, and it also participated in the rostral formation of vertebrates. 17 Slavotinek et al reported that Vax1 mutation is associated with human cleft lip and palate, absence of the pineal gland, corpus callosum agenesis, hippocampal malformations and small optic nerves. 18 …”

Developmental programming and lineage branching of early human telencephalon

“…LHX6 , GAD1 , GAD2 , DLX2 , DLX5, and NEUROD2 and NEUROD6 , which are regulators expressed in late‐stage progenitors and neurons, and are required for distinct neuronal differentiation (Bormuth et al , 2013; Kepecs & Fishell, 2014), were present in subpopulations of MGE and PFC, respectively (Figs 1C and EV1F). In contrast, other regional identity genes, such as EN1 and TAL2 for midbrain (Metzakopian et al , 2012), VAX1 for hypothalamus (Hallonet et al , 1998; Wang et al , 2015), and GSX2 , HTR3A , and EBF1 for lateral/caudal ganglionic eminences (LGE/CGE) (Kepecs & Fishell, 2014; Mayer et al , 2018), were not detected (Fig EV1G).…”