Nagai T, Aruga J, Takada S, Günther T, Spörle R, Schughart K, Mikoshiba K
Molecular Neurobiology Laboratory, Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Dev Biol. 1997 Feb 15;182(2):299-313. doi: 10.1006/dbio.1996.8449.
We examined the expression of Zic1, Zic2, and Zic3 genes in the mouse embryo by means of in situ hybridization. Zic genes were found as a group of genes coding for zinc finger proteins that are expressed in a restricted manner in the adult mouse cerebellum. We showed that the genes are the vertebrate homologues of Drosophila odd-paired, which may play an essential role in parasegmental subdivision and in visceral mesoderm development. The expression of the three Zic genes was first detected at gastrulation in a spatially restricted manner. At neurulation, the expression became restricted to the dorsal neural ectoderm and dorsal paraxial mesoderm. During organogenesis, the three genes were expressed in specific regions of several developing organs, including dorsal areas of the brain, spinal cord, paraxial mesenchyme, and epidermis, the marginal zone of the neural retina and distal regions of the developing limb. For all stages, significant differences in the spatial expression of Zic1, Zic2, and Zic3 were observed. Furthermore, the expression of Zic genes in Pax3, Wnt-1, and Wnt-3a mutant embryos suggested that Zic genes are not primarily regulated by the three genes which were expressed in dorsal areas similar to Zic genes. However, in open brain, a mutant with severe neural tube defects, and in the Wnt-3a mutant mice, the expression of Zic genes was changed. The changed expression pattern in Wnt-3a mutant mice suggests that Zic genes in the neural tube are regulated by the factors from notochord. Our findings suggest that Zic genes are involved in many developmental processes. Furthermore, analysis of gene expression patterns in different mouse mutants indicated that Zic genes may act upstream of many known developmental regulatory genes.
我们通过原位杂交技术检测了小鼠胚胎中Zic1、Zic2和Zic3基因的表达。Zic基因是一组编码锌指蛋白的基因，在成年小鼠小脑中以受限的方式表达。我们发现这些基因是果蝇odd-paired的脊椎动物同源基因，可能在副节段细分和内脏中胚层发育中起重要作用。这三个Zic基因的表达首先在原肠胚形成期以空间受限的方式被检测到。在神经胚形成期，表达局限于背侧神经外胚层和背侧轴旁中胚层。在器官发生过程中，这三个基因在几个发育器官的特定区域表达，包括脑的背侧区域、脊髓、轴旁间充质和表皮、神经视网膜的边缘区以及发育肢体的远端区域。在所有阶段，均观察到Zic1、Zic2和Zic3在空间表达上存在显著差异。此外，Zic基因在Pax3、Wnt-1和Wnt-3a突变胚胎中的表达表明，Zic基因并非主要受这三个在与Zic基因相似的背侧区域表达的基因调控。然而，在患有严重神经管缺陷的open brain突变体以及Wnt-3a突变小鼠中，Zic基因的表达发生了变化。Wnt-3a突变小鼠中表达模式的改变表明，神经管中的Zic基因受来自脊索的因子调控。我们的研究结果表明，Zic基因参与了许多发育过程。此外，对不同小鼠突变体中基因表达模式的分析表明，Zic基因可能在许多已知的发育调控基因的上游起作用。
