Conserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: evidence from targeted mutations.
The development of two major subdivisions of the vertebrate nervous system, the midbrain and the cerebellum, is controlled by signals emanating from a constriction in the neural primordium called the midbrain/hindbrain organizer (Joyner, A. L. (1996) Trends Genet. 12, 15-201). The closely related transcription factors Pax-2 and Pax-5 exhibit an overlapping expression pattern very early in the developing midbrain/hindbrain junction. Experiments carried out in fish (Krauss, S., Maden, M., Holder, N. & Wilson, S. W. (1992) Nature (London) 360, 87-89) with neutralizing antibodies against Pax-b, the orthologue of Pax-2 in mouse, placed this gene family in an regulatory cascade necessary for the development of the midbrain and the cerebellum. The targeted mutation of Pax-5 has been reported to have only slight effects in the development of structures derived from the isthmic constriction, whereas the Pax-2 null mutant mice show a background-dependent phenotype with varying penetrance. To test a possible redundant function between Pax-2 and Pax-5 we analyzed the brain phenotypes of mice expressing different dosages of both genes. Our results demonstrate a conserved biological function of both proteins in midbrain/hindbrain regionalization. Additionally, we show that one allele of Pax-2, but not Pax-5, is necessary and sufficient for midbrain and cerebellum development in C57BL/6 mice.
Schwarz
M
M
Max Planck Institute for Biophysical Chemistry, Am Fassberg 37077 Göttingen, Germany.
Alvarez-Bolado
G
G
Urbánek
P
P
Busslinger
M
M
Gruss
P
P
D000818:Animals; D002531:Cerebellum / Q000196:embryology* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005314:Embryonic and Fetal Development; D018390:Gene Targeting; D008636:Mesencephalon / Q000196:embryology* / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009687:Nuclear Proteins / Q000502:physiology*; D051762:PAX2 Transcription Factor; D051757:PAX5 Transcription Factor; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; D051757:PAX5 Transcription Factor; C497319:Pax2 protein, mouse; C497282:Pax5 protein, mouse; D014157:Transcription Factors