Leal S M, Qian L, Lacin H, Bodmer R, Skeath J B
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Dev Biol. 2009 Jan 1;325(1):138-50. doi: 10.1016/j.ydbio.2008.10.006. Epub 2008 Nov 1.
T-box genes encode a large family of transcription factors that regulate many developmental processes in vertebrates and invertebrates. In addition to their roles in regulating embryonic heart and epidermal development in Drosophila, we provide evidence that the T-box transcription factors neuromancer1 (nmr1) and neuromancer2 (nmr2) play key roles in embryonic CNS development. We verify that nmr1 and nmr2 function in a partially redundant manner to regulate neuronal cell fate by inhibiting even-skipped (eve) expression in specific cells in the CNS. Consistent with their redundant function, nmr1 and nmr2 exhibit overlapping yet distinct protein expression profiles within the CNS. Of note, nmr2 transcript and protein are expressed in identical patterns of segment polarity stripes, defined sets of neuroblasts, many ganglion mother cells and discrete populations of neurons. However, while we observe nmr1 transcripts in segment polarity stripes and specific neural precursors in early stages of CNS development, we first detect Nmr1 protein in later stages of CNS development where it is restricted to discrete subsets of Nmr2-positive neurons. Expression studies identify nearly all Nmr1/2 co-expressing neurons as interneurons, while a single Eve-positive U/CQ motor neuron weakly co-expresses Nmr2. Lineage studies map a subset of Nmr1/2-positive neurons to neuroblast lineages 2-2, 6-1, and 6-2 while genetic studies reveal that nmr2 collaborates with nkx6 to regulate eve expression in the CNS. Thus, nmr1 and nmr2 appear to act together as members of the combinatorial code of transcription factors that govern neuronal subtype identity in the CNS.
T-box基因编码一大类转录因子，这些转录因子调节脊椎动物和无脊椎动物的许多发育过程。除了在调节果蝇胚胎心脏和表皮发育中的作用外，我们还提供证据表明，T-box转录因子神经漫游者1（nmr1）和神经漫游者2（nmr2）在胚胎中枢神经系统发育中起关键作用。我们证实，nmr1和nmr2以部分冗余的方式发挥作用，通过抑制中枢神经系统特定细胞中的偶数跳动（eve）表达来调节神经元细胞命运。与其冗余功能一致，nmr1和nmr2在中枢神经系统内表现出重叠但不同的蛋白质表达谱。值得注意的是，nmr2转录本和蛋白质以相同的节段极性条纹模式表达，这些条纹定义了神经母细胞、许多神经节母细胞和离散神经元群体的特定集合。然而，虽然我们在中枢神经系统发育早期的节段极性条纹和特定神经前体中观察到nmr1转录本，但我们首先在中枢神经系统发育后期检测到Nmr1蛋白，此时它仅限于Nmr2阳性神经元的离散子集。表达研究确定几乎所有共表达Nmr1/2的神经元都是中间神经元，而单个Eve阳性的U/CQ运动神经元弱共表达Nmr2。谱系研究将一部分Nmr1/2阳性神经元映射到神经母细胞谱系2-2、6-1和6-2，而遗传学研究表明，nmr2与nkx6协同调节中枢神经系统中eve的表达。因此，nmr1和nmr2似乎作为转录因子组合密码的成员共同发挥作用，该密码决定了中枢神经系统中神经元亚型的身份。
