Terriente Félix Javier, Magariños Marta, Díaz-Benjumea Fernando J
Centro de Biología Molecular--C.S.I.C., Facultad de Biología, Universidad Autónoma-Cantoblanco, 28049 Madrid, Spain.
Development. 2007 May;134(10):1845-52. doi: 10.1242/dev.003830. Epub 2007 Apr 11.
Nab proteins form an evolutionarily conserved family of transcriptional co-regulators implicated in multiple developmental events in various organisms. They lack DNA-binding domains and act by associating with other transcription factors, but their precise roles in development are not known. Here we analyze the role of nab in Drosophila development. By employing genetic approaches we found that nab is required for proximodistal patterning of the wing imaginal disc and also for determining specific neuronal fates in the embryonic CNS. We identified two partners of Nab: the zinc-finger transcription factors Rotund and Squeeze. Nab is co-expressed with squeeze in a subset of neurons in the embryonic ventral nerve cord and with rotund in a circular domain of the distal-most area of the wing disc. Our results indicate that Nab is a co-activator of Squeeze and is required to limit the number of neurons that express the LIM-homeodomain gene apterous and to specify Tv neuronal fate. Conversely, Nab is a co-repressor of Rotund in wing development and is required to limit the expression of wingless (wg) in the wing hinge, where wg plays a mitogenic role. We also showed by pull-down assays that Nab binds directly to Rotund and Squeeze via its conserved C-terminal domain. We propose two mechanisms by which the activation of wg expression by Rotund in the wing hinge is repressed in the distal wing.
Nab蛋白构成了一个在进化上保守的转录共调节因子家族，参与多种生物体的多个发育事件。它们缺乏DNA结合结构域，通过与其他转录因子结合发挥作用，但其在发育中的精确作用尚不清楚。在这里，我们分析了nab在果蝇发育中的作用。通过采用遗传学方法，我们发现nab对于翅成虫盘的近端到远端模式形成以及确定胚胎中枢神经系统中的特定神经元命运是必需的。我们鉴定出了Nab的两个伙伴：锌指转录因子Rotund和Squeeze。Nab与squeeze在胚胎腹侧神经索的一部分神经元中共同表达，与rotund在翅盘最远端区域的一个圆形区域中共同表达。我们的结果表明，Nab是Squeeze的共激活因子，对于限制表达LIM同源结构域基因apterous的神经元数量以及确定Tv神经元命运是必需的。相反，在翅发育中，Nab是Rotund的共抑制因子，对于限制翅铰链中无翅（wg）的表达是必需的，其中wg发挥促有丝分裂作用。我们还通过下拉实验表明，Nab通过其保守的C末端结构域直接与Rotund和Squeeze结合。我们提出了两种机制，通过这两种机制，Rotund在翅铰链中对wg表达的激活在翅的远端受到抑制。
