Pocock Roger, Mione Marina, Hussain Sagair, Maxwell Sara, Pontecorvi Marco, Aslam Sobia, Gerrelli Dianne, Sowden Jane C, Woollard Alison
Genetics Unit, Biochemistry Department, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Dev Biol. 2008 May 15;317(2):671-85. doi: 10.1016/j.ydbio.2008.02.015. Epub 2008 Feb 21.
The Tbx20 orthologue, mab-9, is required for development of the Caenorhabditis elegans hindgut, whereas several vertebrate Tbx20 genes promote heart development. Here we show that Tbx20 orthologues also have a role in motor neuron development that is conserved between invertebrates and vertebrates. mab-9 mutants exhibit guidance defects in dorsally projecting axons from motor neurons located in the ventral nerve cord. Danio rerio (Zebrafish) tbx20 morphants show defects in the migration patterns of motor neuron soma of the facial and trigeminal motor neuron groups. Human TBX20 is expressed in motor neurons in the developing hindbrain of human embryos and we show that human TBX20 can substitute for zebrafish tbx20 in promoting cranial motor neuron migration. mab-9 is also partially able to rescue the zebrafish migration defect, whereas other vertebrate T-box genes cannot. Conversely we show that the human TBX20 T-box domain can rescue motor neuron defects in C. elegans. These data suggest the functional equivalence of Tbx20 orthologues in regulating the development of specific motor neuron groups. We also demonstrate the functional equivalence of human and C. elegans Tbx20 T-box domains for regulating male tail development in the nematode even though these genes play highly diverged roles in organogenesis.
Tbx20的直系同源基因mab - 9对线虫后肠的发育是必需的，而几种脊椎动物的Tbx20基因则促进心脏发育。在此我们表明，Tbx20直系同源基因在运动神经元发育中也发挥作用，这在无脊椎动物和脊椎动物之间是保守的。mab - 9突变体在位于腹神经索的运动神经元背向投射的轴突中表现出导向缺陷。斑马鱼tbx20的吗啉代反义寡核苷酸注射胚胎显示面部和三叉神经运动神经元组的运动神经元胞体迁移模式存在缺陷。人类TBX20在人类胚胎发育中的后脑运动神经元中表达，并且我们表明人类TBX20在促进颅运动神经元迁移方面可以替代斑马鱼tbx20。mab - 9也部分能够挽救斑马鱼的迁移缺陷，而其他脊椎动物的T - 盒基因则不能。相反，我们表明人类TBX20的T - 盒结构域可以挽救线虫中的运动神经元缺陷。这些数据表明Tbx20直系同源基因在调节特定运动神经元组的发育方面功能等效。我们还证明了人类和线虫Tbx20的T - 盒结构域在调节线虫雄性尾部发育方面功能等效，尽管这些基因在器官发生中发挥着高度不同的作用。
