Integrins are required for cardioblast polarisation in Drosophila

Abstract

BackgroundThe 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.ResultsAs 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.ConclusionOur findings reveal an instructive role for Integrins in communicating polarising information to cells during migration, and during transition to an epithelial tube structure.

Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation

“…In fra 3 /+ heterozygous embryos viewed in cross-section, Dlg localizes to the dorsal and ventral points of CB–CB contact as previously observed for wild type embryos (Medioni et al, 2008; Vanderploeg et al, 2012) (Fig. 3D).…”

TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

“…Interestingly, loss of chromosome 3p, which contains ROBO1 and TGFBR2 genes, is frequently observed in HNSCC [27]. Moreover, ROBO1, in concert with integrins, has been shown to be responsible for cardioblast polarization [28] and regulation of responsiveness to Slit- repellent signals [29]. We therefore aimed to determine the expression of ROBO1 in invasive ECdnT cultures after TGFβ inhibition.…”

“…One such chemorepellent pathway is elicited by ROBO1, which has been shown to participate with SLIT2 in axon guidance and to control breast morphogenesis and tumor invasion [26,72]. ROBO1, a target of TGFβ signaling [26,73], is a receptor that together with integrins can regulate cardioblast polarization [28] and the responsiveness to SLIT repellent signals [29]. Moreover ROBO1 prevents the chemotactic effect of HGF and SDF-1 in epithelia cells [74,75].…”

Extracellular matrix downregulation in the Drosophila heart preserves contractile function and improves lifespan

“…Pericardin is also essential for tube formation [22, 23] and colocalizes with other BM components on the outer BM surfaces of the heart tube. While BM and integrin expression help polarize cells during development [17, 24], their function in adult Drosophila may be to mechanically couple CMs and VM.…”