Limits...
The first "Slit" is the deepest: the secret to a hollow heart.

Helenius IT, Beitel GJ - J. Cell Biol. (2008)

Bottom Line: Kramer. 2008.In addition, the two groups demonstrate that heart lumen formation is even more distinct from typical epithelial tubulogenesis mechanisms because the heart lumen is bounded by membrane surfaces that have basal rather than apical attributes.As the D. melanogaster cardioblasts are thought to have significant evolutionary similarity to vertebrate endothelial and cardiac lineages, these findings are likely to provide insights into mechanisms of vertebrate heart and vascular morphogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.

ABSTRACT
Tubular organs are essential for life, but lumen formation in nonepithelial tissues such as the vascular system or heart is poorly understood. Two studies in this issue (Medioni, C., M. Astier, M. Zmojdzian, K. Jagla, and M. Sémériva. 2008. J. Cell Biol. 182:249-261; Santiago-Martínez, E., N.H. Soplop, R. Patel, and S.G. Kramer. 2008. J. Cell Biol. 182:241-248) reveal unexpected roles for the Slit-Robo signaling system during Drosophila melanogaster heart morphogenesis. In cardioblasts, Slit and Robo modulate the cell shape changes and domains of E-cadherin-based adhesion that drive lumen formation. Furthermore, in contrast to the well-known paracrine role of Slit and Robo in guiding cell migrations, here Slit and Robo may act by autocrine signaling. In addition, the two groups demonstrate that heart lumen formation is even more distinct from typical epithelial tubulogenesis mechanisms because the heart lumen is bounded by membrane surfaces that have basal rather than apical attributes. As the D. melanogaster cardioblasts are thought to have significant evolutionary similarity to vertebrate endothelial and cardiac lineages, these findings are likely to provide insights into mechanisms of vertebrate heart and vascular morphogenesis.

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Slit, Robo, and E-cadherin play key roles in D. melanogaster heart tube lumen formation. (A) Schematic cross section of two wild-type cardioblasts with distinct membrane domains apposing first at their dorsal adhesive/junctional regions (“J” domains) and then ventrally to encapsulate a central lumen bounded by the lumenal membrane (“L” domain) that expresses Slit, Robo, and dystroglycan. (B) When Slit–Robo signaling is compromised, either no lumen or a small mislocalized lumen forms. (C) Because each cardioblast expresses both Slit and Robo, signaling to antagonize E-cadherin–based adhesion may be paracrine, autocrine, or both. (D) Slit and Robo appear to be involved in at least three distinct processes required for a lumen of the correct shape to form at the correct location. E-Cad, E-cadherin; GOF, gain of function; LOF, loss of function.
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fig1: Slit, Robo, and E-cadherin play key roles in D. melanogaster heart tube lumen formation. (A) Schematic cross section of two wild-type cardioblasts with distinct membrane domains apposing first at their dorsal adhesive/junctional regions (“J” domains) and then ventrally to encapsulate a central lumen bounded by the lumenal membrane (“L” domain) that expresses Slit, Robo, and dystroglycan. (B) When Slit–Robo signaling is compromised, either no lumen or a small mislocalized lumen forms. (C) Because each cardioblast expresses both Slit and Robo, signaling to antagonize E-cadherin–based adhesion may be paracrine, autocrine, or both. (D) Slit and Robo appear to be involved in at least three distinct processes required for a lumen of the correct shape to form at the correct location. E-Cad, E-cadherin; GOF, gain of function; LOF, loss of function.

Mentions: The D. melanogaster heart is a comparatively simple structure consisting of two parallel rows of myoendothelial cardioblasts (CBs) enclosing a solitary lumen. As in human heart formation, D. melanogaster CBs migrate to the future location of the heart. In a process that requires the well-known Slit–Robo guidance system (for review see Dickson and Gilestro, 2006), CBs organize into two parallel rows that converge at the dorsal midline, just below the epidermis. Near the end of the migratory phase, these initially mesenchymal cells polarize, but, strikingly, they do not establish a typical epithelial polarity. Instead, they establish a unique polarity along the dorsal/ventral axis (Fig. 1). As CBs meet at the midline, they form a tube by apposing their dorsal and ventral edges with the corresponding CB of the opposing row, thus encapsulating a lumen (Fig. 1 A; for review see Tao and Schulz, 2007). This “appositional” mechanism of tube formation is not typically used during epithelial organogenesis, which generally involves deformation of an existing apical surface by invagination or budding, or formation of a new apical (lumenal) surface by cavitation or vesicular fusion (for reviews see Hogan and Kolodziej, 2002; Lubarsky and Krasnow, 2003). Although recent papers have investigated the genes and pathways required for proper migration and organization of CBs into neatly apposed rows (Qian et al., 2005; MacMullin and Jacobs, 2006; Santiago-Martinez et al., 2006) and identified several genes required for lumen formation (Yarnitzky and Volk, 1995; Haag et al., 1999), the present studies are important because they define new molecular mechanisms of tubulogenesis and a lumenal membrane with unique polarity.


The first "Slit" is the deepest: the secret to a hollow heart.

Helenius IT, Beitel GJ - J. Cell Biol. (2008)

Slit, Robo, and E-cadherin play key roles in D. melanogaster heart tube lumen formation. (A) Schematic cross section of two wild-type cardioblasts with distinct membrane domains apposing first at their dorsal adhesive/junctional regions (“J” domains) and then ventrally to encapsulate a central lumen bounded by the lumenal membrane (“L” domain) that expresses Slit, Robo, and dystroglycan. (B) When Slit–Robo signaling is compromised, either no lumen or a small mislocalized lumen forms. (C) Because each cardioblast expresses both Slit and Robo, signaling to antagonize E-cadherin–based adhesion may be paracrine, autocrine, or both. (D) Slit and Robo appear to be involved in at least three distinct processes required for a lumen of the correct shape to form at the correct location. E-Cad, E-cadherin; GOF, gain of function; LOF, loss of function.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2483525&req=5

fig1: Slit, Robo, and E-cadherin play key roles in D. melanogaster heart tube lumen formation. (A) Schematic cross section of two wild-type cardioblasts with distinct membrane domains apposing first at their dorsal adhesive/junctional regions (“J” domains) and then ventrally to encapsulate a central lumen bounded by the lumenal membrane (“L” domain) that expresses Slit, Robo, and dystroglycan. (B) When Slit–Robo signaling is compromised, either no lumen or a small mislocalized lumen forms. (C) Because each cardioblast expresses both Slit and Robo, signaling to antagonize E-cadherin–based adhesion may be paracrine, autocrine, or both. (D) Slit and Robo appear to be involved in at least three distinct processes required for a lumen of the correct shape to form at the correct location. E-Cad, E-cadherin; GOF, gain of function; LOF, loss of function.
Mentions: The D. melanogaster heart is a comparatively simple structure consisting of two parallel rows of myoendothelial cardioblasts (CBs) enclosing a solitary lumen. As in human heart formation, D. melanogaster CBs migrate to the future location of the heart. In a process that requires the well-known Slit–Robo guidance system (for review see Dickson and Gilestro, 2006), CBs organize into two parallel rows that converge at the dorsal midline, just below the epidermis. Near the end of the migratory phase, these initially mesenchymal cells polarize, but, strikingly, they do not establish a typical epithelial polarity. Instead, they establish a unique polarity along the dorsal/ventral axis (Fig. 1). As CBs meet at the midline, they form a tube by apposing their dorsal and ventral edges with the corresponding CB of the opposing row, thus encapsulating a lumen (Fig. 1 A; for review see Tao and Schulz, 2007). This “appositional” mechanism of tube formation is not typically used during epithelial organogenesis, which generally involves deformation of an existing apical surface by invagination or budding, or formation of a new apical (lumenal) surface by cavitation or vesicular fusion (for reviews see Hogan and Kolodziej, 2002; Lubarsky and Krasnow, 2003). Although recent papers have investigated the genes and pathways required for proper migration and organization of CBs into neatly apposed rows (Qian et al., 2005; MacMullin and Jacobs, 2006; Santiago-Martinez et al., 2006) and identified several genes required for lumen formation (Yarnitzky and Volk, 1995; Haag et al., 1999), the present studies are important because they define new molecular mechanisms of tubulogenesis and a lumenal membrane with unique polarity.

Bottom Line: Kramer. 2008.In addition, the two groups demonstrate that heart lumen formation is even more distinct from typical epithelial tubulogenesis mechanisms because the heart lumen is bounded by membrane surfaces that have basal rather than apical attributes.As the D. melanogaster cardioblasts are thought to have significant evolutionary similarity to vertebrate endothelial and cardiac lineages, these findings are likely to provide insights into mechanisms of vertebrate heart and vascular morphogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.

ABSTRACT
Tubular organs are essential for life, but lumen formation in nonepithelial tissues such as the vascular system or heart is poorly understood. Two studies in this issue (Medioni, C., M. Astier, M. Zmojdzian, K. Jagla, and M. Sémériva. 2008. J. Cell Biol. 182:249-261; Santiago-Martínez, E., N.H. Soplop, R. Patel, and S.G. Kramer. 2008. J. Cell Biol. 182:241-248) reveal unexpected roles for the Slit-Robo signaling system during Drosophila melanogaster heart morphogenesis. In cardioblasts, Slit and Robo modulate the cell shape changes and domains of E-cadherin-based adhesion that drive lumen formation. Furthermore, in contrast to the well-known paracrine role of Slit and Robo in guiding cell migrations, here Slit and Robo may act by autocrine signaling. In addition, the two groups demonstrate that heart lumen formation is even more distinct from typical epithelial tubulogenesis mechanisms because the heart lumen is bounded by membrane surfaces that have basal rather than apical attributes. As the D. melanogaster cardioblasts are thought to have significant evolutionary similarity to vertebrate endothelial and cardiac lineages, these findings are likely to provide insights into mechanisms of vertebrate heart and vascular morphogenesis.

Show MeSH
Related in: MedlinePlus