Matise M P, Joyner A L
New York University Medical School, Skirball Institute of Biomolecular Medicine, Developmental Genetics Program, New York, New York 10016, USA.
J Neurosci. 1997 Oct 15;17(20):7805-16. doi: 10.1523/JNEUROSCI.17-20-07805.1997.
The vertebrate spinal cord has long served as a useful system for studying the pattern of cell differentiation along the dorsoventral (d/v) axis. In this paper, we have defined the expression of several classes of genes expressed in restricted d/v domains in the intermediate region (IR) of the mouse spinal cord, in which most interneurons are generated. From this analysis, we have found that spinal cord interneurons and their precursors express unique combinations of transcription factors and Notch ligands at the onset of their differentiation. The domains of expression of a number of different classes of genes share similar boundaries, indicating that there could be a basic subdivision of the ventral IR into four distinct regions. This differential gene expression suggests that spinal cord interneurons acquire unique identities early in their development and that Notch signaling mechanisms may participate in the determination of cell fate along the d/v axis. Gene expression studies in Engrailed-1 (En-1) mutants showed that En-1-expressing and other closely positioned classes of neurons do not require the homeodomain protein En-1 for their early pattern of differentiation. Rather, it is suggested that En-1 may function to distinguish a subset of interneurons during the later maturation of the spinal cord.
长期以来,脊椎动物的脊髓一直是研究沿背腹(d/v)轴细胞分化模式的有用系统。在本文中,我们确定了在小鼠脊髓中间区域(IR)中沿背腹受限区域表达的几类基因的表达情况,大多数中间神经元在此区域产生。通过该分析,我们发现脊髓中间神经元及其前体在分化开始时表达独特的转录因子和Notch配体组合。许多不同类别的基因表达域具有相似的边界,这表明腹侧IR可能基本细分为四个不同区域。这种差异基因表达表明脊髓中间神经元在其发育早期获得独特的身份,并且Notch信号机制可能参与沿d/v轴的细胞命运决定。对Engrailed-1(En-1)突变体的基因表达研究表明,表达En-1的神经元和其他位置相近的神经元类别在其早期分化模式中不需要同源域蛋白En-1。相反,有人提出En-1可能在脊髓后期成熟过程中发挥作用,以区分中间神经元的一个子集。