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 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.
Hallonet
M
M
Department of Developmental Biochemistry, University of Göttingen, Institute for Biochemistry, 37073 Göttingen, Germany.
Hollemann
T
T
Pieler
T
T
Gruss
P
P
D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000502:physiology*; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics; D003103:Coloboma / Q000196:embryology / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000235:genetics; D005136:Eye Proteins; D018390:Gene Targeting; D005801:Genes, Homeobox; D005804:Genes, Lethal; D005816:Genetic Complementation Test; D053823:Hedgehog Proteins; D016142:Holoprosencephaly / Q000196:embryology / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008845:Microinjections; D009024:Morphogenesis / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D009900:Optic Nerve / Q000002:abnormalities / Q000196:embryology; D051762:PAX2 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D016548:Prosencephalon / Q000196:embryology*; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014795:Visual Pathways / Q000196:embryology*; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009479:Neuropeptides; D051762:PAX2 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C497319:Pax2 protein, mouse; C000605732:Pax6 protein, mouse; D011506:Proteins; C105441:Rax protein, mouse; D012097:Repressor Proteins; C111251:Rx protein, vertebrate; D015534:Trans-Activators; D014157:Transcription Factors; C113864:Vax1 protein, Xenopus; C485177:Vax1 protein, mouse; D029867:Xenopus Proteins