Rebagliati M R, Toyama R, Haffter P, Dawid I B
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9932-7. doi: 10.1073/pnas.95.17.9932.
Ventral structures in the central nervous system are patterned by signals emanating from the underlying mesoderm as well as originating within the neuroectoderm. Mutations in the zebrafish, Danio rerio, are proving instrumental in dissecting these midline signals. The cyclops mutation leads to a loss of medial floor plate and to severe deficits in ventral forebrain development, leading to cyclopia. Here, we report that the cyclops locus encodes the nodal-related protein Ndr2, a member of the transforming growth factor type beta superfamily of factors. The evidence includes identification of a missense mutation in the initiation codon and rescue of the cyclops phenotype by expression of ndr2 RNA, here renamed "cyclops." Thus, in interaction with other molecules implicated in these processes such as sonic hedgehog and one-eyed-pinhead, cyclops is required for ventral midline patterning of the embryonic central nervous system.
中枢神经系统中的腹侧结构由源自下方中胚层以及神经外胚层内部产生的信号形成模式。斑马鱼(Danio rerio)中的突变正有助于剖析这些中线信号。独眼畸形突变导致内侧底板缺失以及腹侧前脑发育严重缺陷,进而导致独眼畸形。在此,我们报告独眼畸形基因座编码节点相关蛋白Ndr2,它是转化生长因子β超家族因子的成员之一。证据包括起始密码子中错义突变的鉴定以及通过表达ndr2 RNA(此处重新命名为“独眼畸形”)拯救独眼畸形表型。因此,与这些过程中涉及的其他分子(如音猬因子和单眼针头蛋白)相互作用时,独眼畸形对于胚胎中枢神经系统的腹侧中线模式形成是必需的。