Schwarz M, Alvarez-Bolado G, Urbánek P, Busslinger M, Gruss P
Max Planck Institute for Biophysical Chemistry, Am Fassberg 37077 Göttingen, Germany.
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14518-23. doi: 10.1073/pnas.94.26.14518.
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.
脊椎动物神经系统的两个主要亚区，即中脑和小脑的发育，受神经原基中一个称为中脑/后脑组织者的缩窄处发出的信号控制（乔伊纳，A. L.（1996年）《遗传学趋势》12卷，第15 - 201页）。密切相关的转录因子Pax - 2和Pax - 5在发育中的中脑/后脑交界处很早就呈现出重叠的表达模式。在鱼类中进行的实验（克劳斯，S.、马登，M.、霍尔德，N.和威尔逊，S. W.（1992年）《自然》（伦敦）360卷，第87 - 89页）使用针对小鼠中Pax - 2的直系同源物Pax - b的中和抗体，将这个基因家族置于中脑和小脑发育所必需的调控级联中。据报道，Pax - 5的靶向突变对源自峡部缩窄的结构发育只有轻微影响，而Pax - 2基因敲除突变小鼠表现出具有不同外显率的背景依赖性表型。为了测试Pax - 2和Pax - 5之间可能的冗余功能，我们分析了表达这两个基因不同剂量的小鼠的脑表型。我们的结果证明了这两种蛋白质在中脑/后脑区域化中具有保守的生物学功能。此外，我们表明在C57BL / 6小鼠中，一个Pax - 2等位基因，而非Pax - 5等位基因，对于中脑和小脑发育是必要且充分的。
