Limits...
Genetic control of cell morphogenesis during Drosophila melanogaster cardiac tube formation.

Medioni C, Astier M, Zmojdzian M, Jagla K, Sémériva M - J. Cell Biol. (2008)

Bottom Line: Our study of cell behavior using three-dimensional and time-lapse imaging and the distribution of cell polarity markers reveals a new mechanism of tubulogenesis in which repulsion of prepatterned luminal domains with basal membrane properties and cell shape remodeling constitute the main driving forces.From these data we propose a model for D. melanogaster cardiac lumen formation, which differs, both at a cellular and molecular level, from current models of epithelial tubulogenesis.We suggest that this new example of tube formation may be helpful in studying vertebrate heart tube formation and primary vasculogenesis.

View Article: PubMed Central - PubMed

Affiliation: Institut de Biologie du Développement de Marseille-Luminy, Centre National de la Recherche Scientifique UMR 6216, Université de la Méditerranée, 13288 Marseille, Cedex 9, France.

ABSTRACT
Tubulogenesis is an essential component of organ development, yet the underlying cellular mechanisms are poorly understood. We analyze here the formation of the Drosophila melanogaster cardiac lumen that arises from the migration and subsequent coalescence of bilateral rows of cardioblasts. Our study of cell behavior using three-dimensional and time-lapse imaging and the distribution of cell polarity markers reveals a new mechanism of tubulogenesis in which repulsion of prepatterned luminal domains with basal membrane properties and cell shape remodeling constitute the main driving forces. Furthermore, we identify a genetic pathway in which roundabout, slit, held out wings, and dystroglycan control cardiac lumen formation by establishing nonadherent luminal membranes and regulating cell shape changes. From these data we propose a model for D. melanogaster cardiac lumen formation, which differs, both at a cellular and molecular level, from current models of epithelial tubulogenesis. We suggest that this new example of tube formation may be helpful in studying vertebrate heart tube formation and primary vasculogenesis.

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Ultrastructure of slit2 mutant CBs. (A–F) Transverse ultra-thin sections of wild-type (A) and slit2 mutant embryos (B–F) at late stage 17. (C–F) Ultra-thin sections at different levels along the AP axis, with C the most anterior and F the most posterior. (C′–F′) High magnifications of C–F showing the extending cell–cell contact between the CBs of the opposite rows (yellow arrows), compared with the wild type (A). (B–F) In slit2 mutant embryos, CBs have a much more rounded shape than in wild-type embryos (A) and the lumen is not formed. (C′ and D′) Note that in slit2 mutants, the contact between CBs often shows interruptions where some vacuolelike structures are observed (blue arrows). L, lumen; CB, cardioblast; N, nucleus; yellow arrows, cell–cell contact; black arrowheads, hemi-adherens junctions; red arrowheads, adherens junction; asterisks, basement membrane. Bars, 1 μm.
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fig3: Ultrastructure of slit2 mutant CBs. (A–F) Transverse ultra-thin sections of wild-type (A) and slit2 mutant embryos (B–F) at late stage 17. (C–F) Ultra-thin sections at different levels along the AP axis, with C the most anterior and F the most posterior. (C′–F′) High magnifications of C–F showing the extending cell–cell contact between the CBs of the opposite rows (yellow arrows), compared with the wild type (A). (B–F) In slit2 mutant embryos, CBs have a much more rounded shape than in wild-type embryos (A) and the lumen is not formed. (C′ and D′) Note that in slit2 mutants, the contact between CBs often shows interruptions where some vacuolelike structures are observed (blue arrows). L, lumen; CB, cardioblast; N, nucleus; yellow arrows, cell–cell contact; black arrowheads, hemi-adherens junctions; red arrowheads, adherens junction; asterisks, basement membrane. Bars, 1 μm.

Mentions: The in vivo observations have been confirmed by an electron microscopy analysis of wild-type and slit2 mutant cardiac tubes showing the lack of cell shape changes in slit2 mutant CBs, which, in contrast to wild-type CBs, display a round shape (Fig. 3, compare B with A). The progressive shrinking of the CB cytoplasm at the site of initial cell–cell contact, which contributes to the lumen formation in wild type, is strongly affected (Fig. 3 A and Fig. S1 [available at http://www.jcb.org/cgi/content/full/jcb.200801100/DC1], yellow arrows, compared with Fig. 3 B). Cell–cell contacts between the two opposite CBs spread over a much larger area than in the wild-type situation. This extended area of cell–cell contact in slit2 mutant embryos is most probably caused by the lack of cell shape remodeling in the absence of slit function. Electron-dense dots corresponding to adherens junctions between two CBs are detected in slit2 mutants (Fig. 3, D′ and E′) in the same position as in the wild type (Fig. S1 B), indicating that slit mutants are able to differentiate cell junctions. This general phenotype is recovered along the entire anterior–posterior axis, at least in the region where the two rows of cells have coalesced (Fig. 3, C–F). However, slight variation in this general phenotype is observed consisting essentially of interruptions in the firm cell–cell contacts between CBs that sometimes form vacuolelike structures inside the CB cytoplasm (Fig. 3, B–F, blue arrows). Similar structures are also observed at early stages in wild-type embryos (Fig. S1 A, blue arrows).


Genetic control of cell morphogenesis during Drosophila melanogaster cardiac tube formation.

Medioni C, Astier M, Zmojdzian M, Jagla K, Sémériva M - J. Cell Biol. (2008)

Ultrastructure of slit2 mutant CBs. (A–F) Transverse ultra-thin sections of wild-type (A) and slit2 mutant embryos (B–F) at late stage 17. (C–F) Ultra-thin sections at different levels along the AP axis, with C the most anterior and F the most posterior. (C′–F′) High magnifications of C–F showing the extending cell–cell contact between the CBs of the opposite rows (yellow arrows), compared with the wild type (A). (B–F) In slit2 mutant embryos, CBs have a much more rounded shape than in wild-type embryos (A) and the lumen is not formed. (C′ and D′) Note that in slit2 mutants, the contact between CBs often shows interruptions where some vacuolelike structures are observed (blue arrows). L, lumen; CB, cardioblast; N, nucleus; yellow arrows, cell–cell contact; black arrowheads, hemi-adherens junctions; red arrowheads, adherens junction; asterisks, basement membrane. Bars, 1 μm.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2483531&req=5

fig3: Ultrastructure of slit2 mutant CBs. (A–F) Transverse ultra-thin sections of wild-type (A) and slit2 mutant embryos (B–F) at late stage 17. (C–F) Ultra-thin sections at different levels along the AP axis, with C the most anterior and F the most posterior. (C′–F′) High magnifications of C–F showing the extending cell–cell contact between the CBs of the opposite rows (yellow arrows), compared with the wild type (A). (B–F) In slit2 mutant embryos, CBs have a much more rounded shape than in wild-type embryos (A) and the lumen is not formed. (C′ and D′) Note that in slit2 mutants, the contact between CBs often shows interruptions where some vacuolelike structures are observed (blue arrows). L, lumen; CB, cardioblast; N, nucleus; yellow arrows, cell–cell contact; black arrowheads, hemi-adherens junctions; red arrowheads, adherens junction; asterisks, basement membrane. Bars, 1 μm.
Mentions: The in vivo observations have been confirmed by an electron microscopy analysis of wild-type and slit2 mutant cardiac tubes showing the lack of cell shape changes in slit2 mutant CBs, which, in contrast to wild-type CBs, display a round shape (Fig. 3, compare B with A). The progressive shrinking of the CB cytoplasm at the site of initial cell–cell contact, which contributes to the lumen formation in wild type, is strongly affected (Fig. 3 A and Fig. S1 [available at http://www.jcb.org/cgi/content/full/jcb.200801100/DC1], yellow arrows, compared with Fig. 3 B). Cell–cell contacts between the two opposite CBs spread over a much larger area than in the wild-type situation. This extended area of cell–cell contact in slit2 mutant embryos is most probably caused by the lack of cell shape remodeling in the absence of slit function. Electron-dense dots corresponding to adherens junctions between two CBs are detected in slit2 mutants (Fig. 3, D′ and E′) in the same position as in the wild type (Fig. S1 B), indicating that slit mutants are able to differentiate cell junctions. This general phenotype is recovered along the entire anterior–posterior axis, at least in the region where the two rows of cells have coalesced (Fig. 3, C–F). However, slight variation in this general phenotype is observed consisting essentially of interruptions in the firm cell–cell contacts between CBs that sometimes form vacuolelike structures inside the CB cytoplasm (Fig. 3, B–F, blue arrows). Similar structures are also observed at early stages in wild-type embryos (Fig. S1 A, blue arrows).

Bottom Line: Our study of cell behavior using three-dimensional and time-lapse imaging and the distribution of cell polarity markers reveals a new mechanism of tubulogenesis in which repulsion of prepatterned luminal domains with basal membrane properties and cell shape remodeling constitute the main driving forces.From these data we propose a model for D. melanogaster cardiac lumen formation, which differs, both at a cellular and molecular level, from current models of epithelial tubulogenesis.We suggest that this new example of tube formation may be helpful in studying vertebrate heart tube formation and primary vasculogenesis.

View Article: PubMed Central - PubMed

Affiliation: Institut de Biologie du Développement de Marseille-Luminy, Centre National de la Recherche Scientifique UMR 6216, Université de la Méditerranée, 13288 Marseille, Cedex 9, France.

ABSTRACT
Tubulogenesis is an essential component of organ development, yet the underlying cellular mechanisms are poorly understood. We analyze here the formation of the Drosophila melanogaster cardiac lumen that arises from the migration and subsequent coalescence of bilateral rows of cardioblasts. Our study of cell behavior using three-dimensional and time-lapse imaging and the distribution of cell polarity markers reveals a new mechanism of tubulogenesis in which repulsion of prepatterned luminal domains with basal membrane properties and cell shape remodeling constitute the main driving forces. Furthermore, we identify a genetic pathway in which roundabout, slit, held out wings, and dystroglycan control cardiac lumen formation by establishing nonadherent luminal membranes and regulating cell shape changes. From these data we propose a model for D. melanogaster cardiac lumen formation, which differs, both at a cellular and molecular level, from current models of epithelial tubulogenesis. We suggest that this new example of tube formation may be helpful in studying vertebrate heart tube formation and primary vasculogenesis.

Show MeSH
Related in: MedlinePlus