Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system

The novel homeobox-containing gene Vax1, a member of the Emx/Not gene famil y, is specifically expressed in the developing basal forebrain and optic ne rve. Here, we show that Vax1 is essential for normal development of these s tructures. Mice carrying a targeted mutation of Vax1 show dysgenesis of the optic nerve, coloboma, defects in the basal telencephalon, and lobar holop rosencephaly. With the help of molecular markers we determined that in the developing visual system, the absence of Vax1 results in a proximal expansi on of the activity of Pax6 and Rx. This observation suggests that Vax1 may interfere negatively with the expression of Pax6 and Rx. In reciprocal gain -of-function experiments, injection of Xvax1 mRNA or Shh into Xenopus embry os primarily affects the brain at the level of the eye primordium. Consiste nt with the loss-of-function results, the injection of Xvax1 results in a d own-regulation of Rx. Similarly, Shh injection expands the Vax1 and Pax2 te rritory at the expense of the Pax6 and Rx region. On the basis of these res ults, we propose a model for a molecular cascade involved in the establishm ent of structures of the visual system.