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

  1. Marc Hallonet,
  2. Thomas Hollemann,
  3. Tomas Pieler, and
  4. Peter Gruss
  1. Department of Molecular and Cell Biology, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Department of Developmental Biochemistry, University of Göttingen, Institute for Biochemistry, 37073 Göttingen, Germany

Abstract

The novel homeobox-containing gene Vax1, a member of theEmx/Not gene family, is specifically expressed in the developing basal forebrain and optic nerve. Here, we show thatVax1 is essential for normal development of these structures. Mice carrying a targeted mutation of Vax1 show dysgenesis of the optic nerve, coloboma, defects in the basal telencephalon, and lobar holoprosencephaly. With the help of molecular markers we determined that in the developing visual system, the absence ofVax1 results in a proximal expansion of the activity ofPax6 and Rx. This observation suggests thatVax1 may interfere negatively with the expression ofPax6 and Rx. In reciprocal gain-of-function experiments, injection of Xvax1 mRNA or Shh intoXenopus embryos primarily affects the brain at the level of the eye primordium. Consistent with the loss-of-function results, the injection of Xvax1 results in a down-regulation of Rx. Similarly, Shh injection expands the Vax1 andPax2 territory at the expense of the Pax6 andRx region. On the basis of these results, we propose a model for a molecular cascade involved in the establishment of structures of the visual system.

Keywords

Footnotes

  • Present address: Institut de Genetique et de Biologie Moleculaire et Cellulaire, Parc d'Innovation, BP 163, 67404 Illkich Cedex, France.

  • Corresponding author.

  • E-MAIL pgruss{at}gwdg.de; FAX 49 551 201 1504.

    • Received April 28, 1999.
    • Accepted October 14, 1999.
| Table of Contents

Life Science Alliance