Vanderploeg Jessica, Vazquez Paz L Lourdes, MacMullin Allison, Jacobs J Roger
Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada.
BMC Dev Biol. 2012 Feb 21;12:8. doi: 10.1186/1471-213X-12-8.
The formation of a tubular organ, such as the heart, requires the communication of positional and polarity signals between migratory cells. Key to this process is the establishment of a new luminal domain on the cell surface, generally from the apical domain of a migratory cell. This domain will also acquire basal properties, as it will produce a luminal extracellular matrix. Integrin receptors are the primary means of cell adhesion and adhesion signaling with the extracellular matrix. Here we characterise the requirement of Integrins in a genetic model of vasculogenesis, the formation of the heart in Drosophila.
As with vertebrates, the Drosophila heart arises from lateral mesoderm that migrates medially to meet their contralateral partners, to then assemble a midline vessel. During migration, Integrins are among the first proteins restricted to the presumptive luminal domain of cardioblasts. Integrins are required for normal levels of leading edge membrane motility. Apical accumulation of Integrins is enhanced by Robo, and reciprocally, apicalisation of luminal factors like Slit and Robo requires Integrin function. Integrins may provide a template for the formation of a lumen by stabilising lumen factors like Robo. Subsequent to migration, Integrin is required for normal cardioblast alignment and lumen formation. This phenotype is most readily modified by other mutations that affect adhesion, such as Talin and extracellular matrix ligands.
Our findings reveal an instructive role for Integrins in communicating polarising information to cells during migration, and during transition to an epithelial tube structure.
管状器官（如心脏）的形成需要迁移细胞之间位置信号和极性信号的传递。这一过程的关键是在细胞表面建立一个新的管腔结构域，通常源自迁移细胞的顶端结构域。该结构域还将获得基底特性，因为它会产生管腔细胞外基质。整合素受体是细胞与细胞外基质黏附及黏附信号传导的主要方式。在此，我们在血管生成的遗传模型（果蝇心脏的形成）中表征整合素的需求。
与脊椎动物一样，果蝇的心脏起源于外侧中胚层，其向内侧迁移以与对侧的细胞会合，进而组装成一条中线血管。在迁移过程中，整合素是最早局限于心成肌细胞假定管腔结构域的蛋白质之一。整合素对于前缘膜正常的运动能力是必需的。Robo增强了整合素的顶端积累，反之，像Slit和Robo这样的管腔因子的顶端化需要整合素功能。整合素可能通过稳定像Robo这样的管腔因子为管腔的形成提供模板。迁移之后，整合素对于心成肌细胞的正常排列和管腔形成是必需的。这种表型最容易被其他影响黏附的突变所改变，如踝蛋白和细胞外基质配体。
我们的研究结果揭示了整合素在迁移过程中以及向上皮管结构转变过程中向细胞传递极化信息方面具有指导作用。
