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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Slit expression in CBs rescues Slit localization and lumen formation in how18 mutants. (A–D) Cardiac tubes of stage 16 embryos stained with Dg (green), Slit (red), and How (blue). A′–D′, Slit only; A″–D″, Dg only. (A–D) On the left are dorsal XY views of wild-type (A and C) and how18 mutant (B and D) embryos; and on the right, transverse Z views of the same cardiac tube. (C and D) Slit overexpression under the control of Hand-Gal4, showing a random distribution of Slit in the cytoplasm of the CBs and of the pericardial cells. Slit is also recovered at the L domain of the CBs. (C) In a wild-type background, Slit overexpression does not affect cardiac lumen formation. Although how18 mutant CBs (B) show a strongly reduced lumen and an absence of Slit at the L domain (Fig. 8, I–M), Slit overexpression in this how18 mutant CBs (D) restores lumen formation and Slit localization at the L domain (in addition to its strong expression in the cytoplasm and pericardial cells because of its overexpression). Dashed circles delimit the lumen. (E) A cartoon showing Slit localization and the cardiac lumen in the different conditions depicted in A–D: wild-type (A), how18 mutant (B), Slit overexpression in a wild-type background (C), and Slit overexpression in a how18 mutant background (D). Bars: (all panels except B) 5 μm; (B) 4 μm.
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fig9: Slit expression in CBs rescues Slit localization and lumen formation in how18 mutants. (A–D) Cardiac tubes of stage 16 embryos stained with Dg (green), Slit (red), and How (blue). A′–D′, Slit only; A″–D″, Dg only. (A–D) On the left are dorsal XY views of wild-type (A and C) and how18 mutant (B and D) embryos; and on the right, transverse Z views of the same cardiac tube. (C and D) Slit overexpression under the control of Hand-Gal4, showing a random distribution of Slit in the cytoplasm of the CBs and of the pericardial cells. Slit is also recovered at the L domain of the CBs. (C) In a wild-type background, Slit overexpression does not affect cardiac lumen formation. Although how18 mutant CBs (B) show a strongly reduced lumen and an absence of Slit at the L domain (Fig. 8, I–M), Slit overexpression in this how18 mutant CBs (D) restores lumen formation and Slit localization at the L domain (in addition to its strong expression in the cytoplasm and pericardial cells because of its overexpression). Dashed circles delimit the lumen. (E) A cartoon showing Slit localization and the cardiac lumen in the different conditions depicted in A–D: wild-type (A), how18 mutant (B), Slit overexpression in a wild-type background (C), and Slit overexpression in a how18 mutant background (D). Bars: (all panels except B) 5 μm; (B) 4 μm.

Mentions: To investigate genetic epistasis between slit, how, and dg, we first analyzed the effects of Slit overexpression in the cardiac tubes of how18 and dg62 homozygous mutant embryos. Remarkably, both Slit localization at the L domain and lumen formation (in 60% of how18 mutants) are rescued by Slit overexpression in the CBs of how18 homozygous mutants (Fig. 9). In contrast, Slit overexpression is not able to rescue lumen formation in dg62 cardiac tubes (not depicted). These results suggest that how acts upstream of slit and that dg functions parallel to slit to control lumen formation.


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)

Slit expression in CBs rescues Slit localization and lumen formation in how18 mutants. (A–D) Cardiac tubes of stage 16 embryos stained with Dg (green), Slit (red), and How (blue). A′–D′, Slit only; A″–D″, Dg only. (A–D) On the left are dorsal XY views of wild-type (A and C) and how18 mutant (B and D) embryos; and on the right, transverse Z views of the same cardiac tube. (C and D) Slit overexpression under the control of Hand-Gal4, showing a random distribution of Slit in the cytoplasm of the CBs and of the pericardial cells. Slit is also recovered at the L domain of the CBs. (C) In a wild-type background, Slit overexpression does not affect cardiac lumen formation. Although how18 mutant CBs (B) show a strongly reduced lumen and an absence of Slit at the L domain (Fig. 8, I–M), Slit overexpression in this how18 mutant CBs (D) restores lumen formation and Slit localization at the L domain (in addition to its strong expression in the cytoplasm and pericardial cells because of its overexpression). Dashed circles delimit the lumen. (E) A cartoon showing Slit localization and the cardiac lumen in the different conditions depicted in A–D: wild-type (A), how18 mutant (B), Slit overexpression in a wild-type background (C), and Slit overexpression in a how18 mutant background (D). Bars: (all panels except B) 5 μm; (B) 4 μm.
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Related In: Results  -  Collection

License 1 - License 2
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fig9: Slit expression in CBs rescues Slit localization and lumen formation in how18 mutants. (A–D) Cardiac tubes of stage 16 embryos stained with Dg (green), Slit (red), and How (blue). A′–D′, Slit only; A″–D″, Dg only. (A–D) On the left are dorsal XY views of wild-type (A and C) and how18 mutant (B and D) embryos; and on the right, transverse Z views of the same cardiac tube. (C and D) Slit overexpression under the control of Hand-Gal4, showing a random distribution of Slit in the cytoplasm of the CBs and of the pericardial cells. Slit is also recovered at the L domain of the CBs. (C) In a wild-type background, Slit overexpression does not affect cardiac lumen formation. Although how18 mutant CBs (B) show a strongly reduced lumen and an absence of Slit at the L domain (Fig. 8, I–M), Slit overexpression in this how18 mutant CBs (D) restores lumen formation and Slit localization at the L domain (in addition to its strong expression in the cytoplasm and pericardial cells because of its overexpression). Dashed circles delimit the lumen. (E) A cartoon showing Slit localization and the cardiac lumen in the different conditions depicted in A–D: wild-type (A), how18 mutant (B), Slit overexpression in a wild-type background (C), and Slit overexpression in a how18 mutant background (D). Bars: (all panels except B) 5 μm; (B) 4 μm.
Mentions: To investigate genetic epistasis between slit, how, and dg, we first analyzed the effects of Slit overexpression in the cardiac tubes of how18 and dg62 homozygous mutant embryos. Remarkably, both Slit localization at the L domain and lumen formation (in 60% of how18 mutants) are rescued by Slit overexpression in the CBs of how18 homozygous mutants (Fig. 9). In contrast, Slit overexpression is not able to rescue lumen formation in dg62 cardiac tubes (not depicted). These results suggest that how acts upstream of slit and that dg functions parallel to slit to control lumen formation.

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