VAX1 IS A NOVEL HOMEOBOX-CONTAINING GENE EXPRESSED IN THE DEVELOPING ANTERIOR VENTRAL FOREBRAIN

The vertebrate forebrain is formed at the rostral end of the neural pl ate under the regulation of local and specific signals emanating from both the endomesoderm and neuroectoderm, The development of the rostra l and ventral forebrain in particular was difficult to study, mainly b ecause 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 expre ssion first occurs in the rostral neural plate, in the medial anterior neural ridge and adjacent ectoderm, Later, at midgestation in the mou se and tadpole stage in Xenopus, the expression remains confined in th e derivatives of this territory which differentiate into rostromedial olfactory placode, optic nerve and disc, and anterior ventral forebrai n, Together, these observations suggest that Vax1 could have an early evolutionary origin and could participate in the specification and for mation 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 st ructure 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 p atterns of these two genes appear complementary in wild-type animals. Vax1 chromosomal location is mapped at the distal end of the mouse chr omosome 19, linked with that of Emx2. These two genes may have arisen by tandem duplication. The Vax1 gene is thus an interesting new tool t o study the rostral ventral forebrain patterning, morphogenesis and ev olution as well as the terminal differentiation of the forebrain in mo use and Xenopus.