Department of Biology, Division of Developmental Biology, Friedrich-Alexander University of Erlangen-Nuremberg, Staudtstr. 5, 91058 Erlangen, Germany.
Dev Biol. 2013 Apr 15;376(2):245-59. doi: 10.1016/j.ydbio.2013.01.022. Epub 2013 Feb 1.
The T-Box family of transcription factors plays fundamental roles in the generation of appropriate spatial and temporal gene expression profiles during cellular differentiation and organogenesis in animals. In this study we report that the Drosophila Tbx1 orthologue optomotor-blind-related-gene-1 (org-1) exerts a pivotal function in the diversification of circular visceral muscle founder cell identities in Drosophila. In embryos mutant for org-1, the specification of the midgut musculature per se is not affected, but the differentiating midgut fails to form the anterior and central midgut constrictions and lacks the gastric caeca. We demonstrate that this phenotype results from the nearly complete loss of the founder cell specific expression domains of several genes known to regulate midgut morphogenesis, including odd-paired (opa), teashirt (tsh), Ultrabithorax (Ubx), decapentaplegic (dpp) and wingless (wg). To address the mechanisms that mediate the regulatory inputs from org-1 towards Ubx, dpp, and wg in these founder cells we genetically dissected known visceral mesoderm specific cis-regulatory-modules (CRMs) of these genes. The analyses revealed that the activities of the dpp and wg CRMs depend on org-1, the CRMs are bound by Org-1 in vivo and their T-Box binding sites are essential for their activation in the visceral muscle founder cells. We conclude that Org-1 acts within a well-defined signaling and transcriptional network of the trunk visceral mesoderm as a crucial founder cell-specific competence factor, in concert with the general visceral mesodermal factor Biniou. As such, it directly regulates several key genes involved in the establishment of morphogenetic centers along the anteroposterior axis of the visceral mesoderm, which subsequently organize the formation of midgut constrictions and gastric caeca and thereby determine the morphology of the midgut.
T 盒转录因子家族在动物细胞分化和器官发生过程中，对适当的空间和时间基因表达谱的产生起着至关重要的作用。在这项研究中，我们报告果蝇 Tbx1 同源物 optomotor-blind-related-gene-1（org-1）在果蝇圆形内脏肌创始细胞身份多样化中发挥关键作用。在 org-1 突变的胚胎中，中肠肌肉的特化本身不受影响，但分化中的中肠不能形成前肠和中央中肠收缩，并且缺乏胃盲囊。我们证明，这种表型是由于几个已知调节中肠形态发生的基因的创始细胞特异性表达域几乎完全丧失，包括 odd-paired（opa）、teashirt（tsh）、Ultrabithorax（Ubx）、decapentaplegic（dpp）和 wingless（wg）。为了解决由 org-1 向这些创始细胞中的 Ubx、dpp 和 wg 传递调节输入的机制，我们在遗传上剖析了这些基因的已知内脏中胚层特异性顺式调控模块（CRMs）。分析表明，dpp 和 wg CRMs 的活性依赖于 org-1，CRMs 在体内被 Org-1 结合，其 T 盒结合位点对于它们在内脏肌创始细胞中的激活是必需的。我们得出结论，Org-1 作为一个关键的创始细胞特异性全能因子，在躯干内脏中胚层的一个明确的信号和转录网络中发挥作用，与一般的内脏中胚层因子 Biniou 协同作用。因此，它直接调节几个参与建立沿内脏中胚层前后轴的形态发生中心的关键基因，随后组织中肠收缩和胃盲囊的形成，并由此决定中肠的形态。
