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Vol. 13, No. 23, pp. 3106-3114, December 1, 1999
1 Department of Molecular and Cell Biology,
Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen,
Germany; 2 Department of Developmental Biochemistry,
University of Göttingen, Institute for Biochemistry, 37073 Göttingen, Germany
The novel homeobox-containing gene Vax1, a member of the
Emx/Not gene family, is specifically expressed in
the developing basal forebrain and optic nerve. Here, we show that
Vax1 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 of
Vax1 results in a proximal expansion 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 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 and
Pax2 territory at the expense of the Pax6 and
Rx 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.
[Key Words: Brain morphogenesis; optic nerve; Pax2; Pax6; Rx; Vax1]
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