Josten Frank, Fuss Bernhard, Feix Maritta, Meissner Torsten, Hoch Michael
Universität Bonn, Institut für Molekulare Physiologie und Entwicklungsbiologie, Abteilung für Molekulare Entwicklungsbiologie, D-53115 Bonn, Germany.
Dev Biol. 2004 Mar 1;267(1):181-9. doi: 10.1016/j.ydbio.2003.11.016.
Temporal and spatial regulation of morphogenesis is pivotal to the formation of organs from simple epithelial tubes. In a genetic screen for novel genes controlling cell movement during posterior foregut development, we have identified and molecularly characterized two alleles of the domeless gene which encodes the Drosophila Janus kinase (JAK)/STAT receptor. We demonstrate that mutants for domeless or any other known component of the canonical JAK/STAT signaling pathway display a failure of coordinated cell movement during the development of the proventriculus, a multiply folded organ which is formed by stereotyped cell rearrangements in the posterior foregut. Whereas the JAK/STAT receptor is expressed in all proventricular precursor cells, expression of upd encoding its ligand and of STAT92E, the signal transducer of the pathway, is locally restricted to cells that invaginate during proventriculus development. We demonstrate by analyzing gene expression mediated by a model Notch response element and by studying the expression of the Notch target gene short stop, which encodes a cytoskeletal crosslinker protein, that JAK/STAT signaling is required for the activation of Notch-dependent gene expression in the foregut. Our results provide strong evidence that JAK/STAT and Notch signaling cooperate in the regulation of target genes that control epithelial morphogenesis in the foregut.
形态发生的时空调控对于从简单上皮管形成器官至关重要。在一项针对控制前肠后部发育过程中细胞运动的新基因的遗传筛选中，我们鉴定并分子表征了无穹顶基因的两个等位基因，该基因编码果蝇Janus激酶（JAK）/信号转导子和转录激活子（STAT）受体。我们证明，无穹顶基因或经典JAK/STAT信号通路的任何其他已知组分的突变体在嗉囊发育过程中表现出协调细胞运动的失败，嗉囊是一个多重折叠的器官，由前肠后部定型的细胞重排形成。虽然JAK/STAT受体在所有嗉囊前体细胞中表达，但其配体upd和该信号通路的信号转导子STAT92E的表达局部限于在嗉囊发育过程中内陷的细胞。通过分析由模型Notch反应元件介导的基因表达以及通过研究Notch靶基因短停的表达（该基因编码一种细胞骨架交联蛋白），我们证明JAK/STAT信号传导对于前肠中Notch依赖性基因表达的激活是必需的。我们的结果提供了强有力的证据，表明JAK/STAT和Notch信号传导在调控控制前肠上皮形态发生的靶基因方面相互协作。
