Saba Rie, Nakatsuji Norio, Saito Tetsuichiro
Department of Genetics, The Graduate University for Advanced Studies, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
J Neurosci. 2003 Mar 15;23(6):1987-91. doi: 10.1523/JNEUROSCI.23-06-01987.2003.
Commissural neurons in the spinal cord project their axons through the floor plate using a number of molecular interactions, such as netrins and their receptor DCC (deleted in colorectal cancer). However, the molecular cascades that control differentiation of commissural neurons are less characterized. A homeobox gene, MBH1 (mammalian BarH1) was expressed specifically in a subset of dorsal cells in the developing spinal cord. Transgenic mice that carried lacZ and MBH1-flanking genome sequences demonstrated that MBH1 was expressed by commissural neurons. To analyze the function of MBH1, we established an in vivo electroporation method for the transfer of DNA into the mouse spinal cord. Ectopic expression of MBH1 drove dorsal cells into the fate of commissural neurons with concomitant expression of TAG-1 (transiently expressed axonal surface glycoprotein 1) and DCC. Cells ectopically expressing MBH1 migrated to the deep dorsal horn, in which endogenous MBH1-positive cells accumulated. These results suggest that MBH1 functions upstream of TAG-1 and DCC and is involved in the fate determination of commissural neurons in the spinal cord.
脊髓中的连合神经元通过多种分子相互作用，如netrins及其受体DCC（结直肠癌缺失基因），将其轴突投射穿过底板。然而，控制连合神经元分化的分子级联反应的特征尚不明确。一个同源盒基因MBH1（哺乳动物BarH1）在发育中的脊髓背侧细胞的一个亚群中特异性表达。携带lacZ和MBH1侧翼基因组序列的转基因小鼠表明MBH1由连合神经元表达。为了分析MBH1的功能，我们建立了一种将DNA导入小鼠脊髓的体内电穿孔方法。MBH1的异位表达使背侧细胞转变为连合神经元的命运，并伴随TAG-1（瞬时表达的轴突表面糖蛋白1）和DCC的表达。异位表达MBH1的细胞迁移到深背角，内源性MBH1阳性细胞在其中积累。这些结果表明，MBH1在TAG-1和DCC的上游起作用，并参与脊髓中连合神经元的命运决定。
