Editors' ChoiceDevelopment

Avoiding a Sticky Situation

See allHide authors and affiliations

Science Signaling  05 Aug 2008:
Vol. 1, Issue 31, pp. ec279
DOI: 10.1126/scisignal.131ec279

The Drosophila heart is formed by two rows of cardioblasts that make dorsal and ventral junctions with their contralateral partners to create the cardiac lumen. Two groups, Santiago-Martínez et al. and Medioni et al., found that the extracellular guidance factor Slit and its receptor Robo played a critical role in this process. Santiago-Martínez et al. performed electron microscopy on Drosophila embryos at stages late in heart development and observed that opposing cardioblasts initiated contact at dorsal regions and underwent a shape change to contact each other ventrally. Immunohistochemical analysis revealed that, like Slit, Robo localized to cardioblast lumenal surfaces. Slit overexpression, which led to its mislocalization as well as that of Robo, caused formation of ectopic lumens between cardioblasts and neighboring cells. Robo overexpression was associated with loss of adhesion between contralateral cardioblasts, whereas cells expressing Robo loss-of-function mutants adhered inappropriately (obliterating the lumen). Conversely, mutation of the gene that encodes E-cadherin eliminated adhesion between contralateral cardioblasts, whereas E-cadherin overexpression led to inappropriate adhesion. Consistent with this, Robo loss-of-function mutants showed increased accumulation of E-cadherin (concentrated at sites of junctional contact in wild-type cardioblasts) in the region of cell apposition. The authors concluded that Slit and Robo promote lumen formation by preventing E-cadherin-mediated adhesion.

Medioni et al., who used in vivo three-dimensional and time-lapse imaging to investigate Drosophila cardiac lumen formation, found that cardioblasts carrying slit or robo/robo2 mutants failed to undergo shape changes that would limit the area of dorsal contact and enable them to make contact ventrally. Instead, they formed an extended contact region with no lumen (or a small ventrally displaced one). Moreover, slit mutants showed an increase in the region in which Armadillo (a marker for the "junctional domain") was found and a decrease in the region in which Dystroglycan (a marker for the "lumenal domain") was found. Thus, the authors conclude that Slit plays a central role in creating the cardiac lumen both by promoting formation of a nonadherent membrane region and by regulating cardioblast shape.

Helenius and Beitel provide thoughtful analysis, noting that localization of Slit and Robo on the same cells may indicate an autocrine function and commenting on differences in membrane polarization between cardioblasts and epithelial cells and in the processes involved in epithelial and cardiac lumen formation.

E. Santiago-Martínez, N. H. Soplop, R. Patel, S. G. Kramer, Repulsion by Slit and Roundabout prevents Shotgun/E-cadherin–mediated cell adhesion during Drosophila heart tube lumen formation. J. Cell Biol. 182, 241-248 (2008). [Abstract] [Full Text]

C. Medioni, M. Astier, M. Zmojdzian, K. Jagla, M. Sémériva, Genetic control of cell morphogenesis during Drosophila melanogaster cardiac tube formation. J. Cell Biol. 182, 249-261 (2008). [Abstract] [Full Text]

I. T. Helenius, G. J. Beitel, The first "Slit" is the deepest: the secret to a hollow heart. J. Cell Biol. 182, 221-223 (2008). [Abstract] [Full Text]

Stay Connected to Science Signaling