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.
Highlights
The formation of a tubular organ, such as the heart, requires the communication of positional and polarity signals between migratory cells
Vascular endothelia are characterised by a polarised cell architecture, wherein Cadherin based cell junctions establish the integrity of the vessel walls, while the lumen of the vessel is defined by Integrins and an extracellular matrix (ECM) [1,2]
We identify a role for the aPS3, bPS1 Integrin dimer in both the early establishment of the apical, pre-luminal domain, as well as a requirement upon Robo for maintained apicalisation of proteins required for lumen formation
Summary
The formation of a tubular organ, such as the heart, requires the communication of positional and polarity signals between migratory cells. Vascular endothelia are characterised by a polarised cell architecture, wherein Cadherin based cell junctions establish the integrity of the vessel walls, while the lumen of the vessel is defined by Integrins and an extracellular matrix (ECM) [1,2]. When these vessels first form, grow or are remodeled, the progenitor cells must be less polarised, as they will change neighbours, migrate through other tissues, and respond to local growth cues. In other contexts, reduced Integrin function is not sufficient to prevent lumen formation, possibly due to the contributions of other ECM factors [2]
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