Millonig J H, Millen K J, Hatten M E
Laboratory of Developmental Neurobiology, The Rockefeller University, New York, New York 10021-6399, USA.
Nature. 2000 Feb 17;403(6771):764-9. doi: 10.1038/35001573.
In the vertebrate central nervous system (CNS), a cascade of signals that originates in the ectoderm adjacent to the neural tube is propagated by the roof plate to dorsalize the neural tube. Here we report that the phenotype of the spontaneous neurological mutant mouse dreher (dr) results from a failure of the roof plate to develop. Dorsalization of the neural tube is consequently affected: dorsal interneurons in the spinal cord and granule neurons in the cerebellar cortex are lost, and the dorsal vertebral neural arches fail to form. Positional cloning of dreher indicates that the LIM homeodomain protein, Lmx1a, is affected in three different alleles of dreher. Lmx1a is expressed in the roof plate along the neuraxis during development of the CNS. Thus, Lmx1a is required for development of the roof plate and, in turn, for specification of dorsal cell fates in the CNS and developing vertebrae.
在脊椎动物的中枢神经系统（CNS）中，起源于神经管相邻外胚层的一系列信号由顶板传播，以使神经管背侧化。我们在此报告，自发神经突变小鼠德雷尔（dreher，dr）的表型是由于顶板发育失败所致。因此，神经管的背侧化受到影响：脊髓中的背侧中间神经元和小脑皮质中的颗粒神经元缺失，并且背侧椎弓未能形成。德雷尔的定位克隆表明，LIM同源域蛋白Lmx1a在德雷尔的三个不同等位基因中受到影响。在中枢神经系统发育过程中，Lmx1a沿神经轴在顶板中表达。因此，Lmx1a是顶板发育所必需的，进而也是中枢神经系统和发育中的椎骨中背侧细胞命运特化所必需的。
