Richard Mélisande, Hoch Michael
Life & Medical Sciences Institute (LIMES) Development, Genetics & Molecular Physiology Unit, University of Bonn, Carl-Troll-Straße, 31, D-53115 Bonn, Germany.
Dev Biol. 2015 Dec 1;408(1):26-40. doi: 10.1016/j.ydbio.2015.10.011. Epub 2015 Oct 9.
Organogenesis relies on specific genetic and molecular programmes, which orchestrate growth and cellular differentiation over developmental time. This is particularly important during Drosophila eye development in which cell-cell inductive events and long-range signalling have to be integrated to regulate proper cell proliferation, differentiation and morphogenesis. How these processes are coordinated is still not very well understood. Here we identify the gap junction protein Innexin2 (Inx2) as an important regulator of eye development. Depleting inx2 during eye development reduces eye size whereas elevating inx2 levels increases eye size. Loss- and gain-of-function experiments demonstrate that inx2 is required functionally in larval eye disc cells where it localises apico-laterally. inx2 regulates disc cell proliferation as well as morphogenetic furrow movement and as a result the amount of differentiated photoreceptors. inx2 interacts genetically with the Dpp pathway and we find that proper activation of the Dpp pathway transducer Mad at the furrow and expression of Dpp receptors Thickveins and Punt in the anterior disc compartment require inx2. We further show that inx2 is required for the transcriptional activation of dpp and punt in the eye disc. Our results highlight the crucial role of gap junction proteins in regulating morphogen-dependent organ size determination.
器官发生依赖于特定的基因和分子程序,这些程序在发育过程中协调生长和细胞分化。这在果蝇眼睛发育过程中尤为重要,其中细胞间诱导事件和长距离信号传导必须整合起来,以调节适当的细胞增殖、分化和形态发生。这些过程是如何协调的,目前仍不太清楚。在这里,我们确定间隙连接蛋白Innexin2(Inx2)是眼睛发育的重要调节因子。在眼睛发育过程中耗尽inx2会减小眼睛大小,而提高inx2水平则会增加眼睛大小。功能丧失和功能获得实验表明,inx2在幼虫眼盘中的细胞功能上是必需的,它定位于顶端外侧。inx2调节眼盘细胞增殖以及形态发生沟的移动,从而调节分化光感受器的数量。inx2与Dpp信号通路存在遗传相互作用,我们发现,在沟处Dpp信号通路转导子Mad的适当激活以及前眼盘隔室中Dpp受体Thickveins和Punt的表达需要inx2。我们进一步表明,inx2是眼盘中dpp和punt转录激活所必需的。我们的结果突出了间隙连接蛋白在调节形态发生素依赖性器官大小决定中的关键作用。