Limits...
Notch and bone morphogenetic protein differentially act on dermomyotome cells to generate endothelium, smooth, and striated muscle.

Ben-Yair R, Kalcheim C - J. Cell Biol. (2008)

Bottom Line: Notch activity is necessary for smooth muscle production while inhibiting striated muscle differentiation, yet it does not affect initial development of endothelial cells.Hence, although different mechanisms are responsible for smooth muscle and endothelium generation, the choice to become smooth versus striated muscle depends on a single signaling system.Altogether, these findings underscore the spatial and temporal complexity of lineage diversification in an apparently homogeneous epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

ABSTRACT
We address the mechanisms underlying generation of skeletal muscle, smooth muscle, and endothelium from epithelial progenitors in the dermomyotome. Lineage analysis shows that of all epithelial domains, the lateral region is the most prolific producer of smooth muscle and endothelium. Importantly, individual labeled lateral somitic cells give rise to only endothelial or mural cells (not both), and endothelial and mural cell differentiation is driven by distinct signaling systems. Notch activity is necessary for smooth muscle production while inhibiting striated muscle differentiation, yet it does not affect initial development of endothelial cells. On the other hand, bone morphogenetic protein signaling is required for endothelial cell differentiation and/or migration but inhibits striated muscle differentiation and fails to impact smooth muscle cell production. Hence, although different mechanisms are responsible for smooth muscle and endothelium generation, the choice to become smooth versus striated muscle depends on a single signaling system. Altogether, these findings underscore the spatial and temporal complexity of lineage diversification in an apparently homogeneous epithelium.

Show MeSH

Related in: MedlinePlus

Inhibition of BMP activity by Noggin affects endothelial but not smooth muscle development. (A and A′) Noggin electroporation into the lateral epithelial somite does not affect cHairy2 expression. Arrowheads delimit the electroporated area. (B) Noggin electroporation into intermediate and lateral plate mesoderms severely inhibits VEGFr2 expression in the lateral somite (arrow). A similar effect was observed upon electroporation of the lateral somite (not depicted). (C) Noggin electroporation into lateral somites reduces the proportion of labeled cells in the myotome 16 h after treatment, compared with control GFP-electroporated somites (P < 0.001), but does not change the proportions of mural or endothelial cells. Results represent mean ± SEM. (D and E) Noggin electroporation (E) into lateral somites alters the differentiation/migration pattern of endothelial cells when compared with control GFP (D). Many QH1-positive cells remain atypically located within the DM epithelium in noggin-treated DMs (arrowheads in E; see G) rather than homing to nascent BVs. (F and G) Lateral somites of E2 embryos were electroporated with Noggin-GFP (G) or control GFP (F). 16 h after treatment, the CV (asterisks) on the treated side exhibits a significant reduction in lumen diameter when compared to the untreated side or to GFP electroporation. Noggin/GFP cells are green. (H) Noggin increases the ratio of mural to endothelial cells in the CV 16 h after electroporation into lateral E2 somites (P = 0.02). Results represent mean ± SEM. QH1 is red and HOECHST is blue in D and E. DA, dorsal aorta; M, myotome; NT, neural tube; WD, Wolffian duct. Bars: (A and A′) 53 μm; (B) 50 μm; (D and E) 43 μm; (F and G) 120 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2234248&req=5

fig6: Inhibition of BMP activity by Noggin affects endothelial but not smooth muscle development. (A and A′) Noggin electroporation into the lateral epithelial somite does not affect cHairy2 expression. Arrowheads delimit the electroporated area. (B) Noggin electroporation into intermediate and lateral plate mesoderms severely inhibits VEGFr2 expression in the lateral somite (arrow). A similar effect was observed upon electroporation of the lateral somite (not depicted). (C) Noggin electroporation into lateral somites reduces the proportion of labeled cells in the myotome 16 h after treatment, compared with control GFP-electroporated somites (P < 0.001), but does not change the proportions of mural or endothelial cells. Results represent mean ± SEM. (D and E) Noggin electroporation (E) into lateral somites alters the differentiation/migration pattern of endothelial cells when compared with control GFP (D). Many QH1-positive cells remain atypically located within the DM epithelium in noggin-treated DMs (arrowheads in E; see G) rather than homing to nascent BVs. (F and G) Lateral somites of E2 embryos were electroporated with Noggin-GFP (G) or control GFP (F). 16 h after treatment, the CV (asterisks) on the treated side exhibits a significant reduction in lumen diameter when compared to the untreated side or to GFP electroporation. Noggin/GFP cells are green. (H) Noggin increases the ratio of mural to endothelial cells in the CV 16 h after electroporation into lateral E2 somites (P = 0.02). Results represent mean ± SEM. QH1 is red and HOECHST is blue in D and E. DA, dorsal aorta; M, myotome; NT, neural tube; WD, Wolffian duct. Bars: (A and A′) 53 μm; (B) 50 μm; (D and E) 43 μm; (F and G) 120 μm.

Mentions: BMP was shown to drive the differentiation of endothelial cells in vitro from embryonic stem cells (Park et al., 2004) and in vivo from the lateral somite (Nimmagadda et al., 2004, 2005). We asked whether it is also important for proper differentiation of the mural lineage. First, we examined whether inhibiting BMP signaling had any effect on expression of hairy2 mRNA. Hairy2 is a transducer of Notch signaling whose mRNA level is stimulated by Notch overexpression (Fig. 2, C and D), an effect accompanied by enhanced mural cell development (Fig. 3). Noggin-DNA was electroporated into the lateral somite of E2 embryos. 12 h after transfection, Noggin-expressing segments exhibited no change in hairy2 levels, suggesting that BMP is not required for mural cell differentiation (n = 5; Fig. 6, A and A′). In contrast, electroporation of noggin-DNA into the lateral mesoderm opposite the segmental plate of E1.5 embryos revealed, 12 h later, a marked reduction of VEGFr2 expression already in the lateral epithelial somite where its expression is maximal (n = 8; Fig. 5 and Fig. 6 B), confirming that BMP is required early during endothelial development.


Notch and bone morphogenetic protein differentially act on dermomyotome cells to generate endothelium, smooth, and striated muscle.

Ben-Yair R, Kalcheim C - J. Cell Biol. (2008)

Inhibition of BMP activity by Noggin affects endothelial but not smooth muscle development. (A and A′) Noggin electroporation into the lateral epithelial somite does not affect cHairy2 expression. Arrowheads delimit the electroporated area. (B) Noggin electroporation into intermediate and lateral plate mesoderms severely inhibits VEGFr2 expression in the lateral somite (arrow). A similar effect was observed upon electroporation of the lateral somite (not depicted). (C) Noggin electroporation into lateral somites reduces the proportion of labeled cells in the myotome 16 h after treatment, compared with control GFP-electroporated somites (P < 0.001), but does not change the proportions of mural or endothelial cells. Results represent mean ± SEM. (D and E) Noggin electroporation (E) into lateral somites alters the differentiation/migration pattern of endothelial cells when compared with control GFP (D). Many QH1-positive cells remain atypically located within the DM epithelium in noggin-treated DMs (arrowheads in E; see G) rather than homing to nascent BVs. (F and G) Lateral somites of E2 embryos were electroporated with Noggin-GFP (G) or control GFP (F). 16 h after treatment, the CV (asterisks) on the treated side exhibits a significant reduction in lumen diameter when compared to the untreated side or to GFP electroporation. Noggin/GFP cells are green. (H) Noggin increases the ratio of mural to endothelial cells in the CV 16 h after electroporation into lateral E2 somites (P = 0.02). Results represent mean ± SEM. QH1 is red and HOECHST is blue in D and E. DA, dorsal aorta; M, myotome; NT, neural tube; WD, Wolffian duct. Bars: (A and A′) 53 μm; (B) 50 μm; (D and E) 43 μm; (F and G) 120 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2234248&req=5

fig6: Inhibition of BMP activity by Noggin affects endothelial but not smooth muscle development. (A and A′) Noggin electroporation into the lateral epithelial somite does not affect cHairy2 expression. Arrowheads delimit the electroporated area. (B) Noggin electroporation into intermediate and lateral plate mesoderms severely inhibits VEGFr2 expression in the lateral somite (arrow). A similar effect was observed upon electroporation of the lateral somite (not depicted). (C) Noggin electroporation into lateral somites reduces the proportion of labeled cells in the myotome 16 h after treatment, compared with control GFP-electroporated somites (P < 0.001), but does not change the proportions of mural or endothelial cells. Results represent mean ± SEM. (D and E) Noggin electroporation (E) into lateral somites alters the differentiation/migration pattern of endothelial cells when compared with control GFP (D). Many QH1-positive cells remain atypically located within the DM epithelium in noggin-treated DMs (arrowheads in E; see G) rather than homing to nascent BVs. (F and G) Lateral somites of E2 embryos were electroporated with Noggin-GFP (G) or control GFP (F). 16 h after treatment, the CV (asterisks) on the treated side exhibits a significant reduction in lumen diameter when compared to the untreated side or to GFP electroporation. Noggin/GFP cells are green. (H) Noggin increases the ratio of mural to endothelial cells in the CV 16 h after electroporation into lateral E2 somites (P = 0.02). Results represent mean ± SEM. QH1 is red and HOECHST is blue in D and E. DA, dorsal aorta; M, myotome; NT, neural tube; WD, Wolffian duct. Bars: (A and A′) 53 μm; (B) 50 μm; (D and E) 43 μm; (F and G) 120 μm.
Mentions: BMP was shown to drive the differentiation of endothelial cells in vitro from embryonic stem cells (Park et al., 2004) and in vivo from the lateral somite (Nimmagadda et al., 2004, 2005). We asked whether it is also important for proper differentiation of the mural lineage. First, we examined whether inhibiting BMP signaling had any effect on expression of hairy2 mRNA. Hairy2 is a transducer of Notch signaling whose mRNA level is stimulated by Notch overexpression (Fig. 2, C and D), an effect accompanied by enhanced mural cell development (Fig. 3). Noggin-DNA was electroporated into the lateral somite of E2 embryos. 12 h after transfection, Noggin-expressing segments exhibited no change in hairy2 levels, suggesting that BMP is not required for mural cell differentiation (n = 5; Fig. 6, A and A′). In contrast, electroporation of noggin-DNA into the lateral mesoderm opposite the segmental plate of E1.5 embryos revealed, 12 h later, a marked reduction of VEGFr2 expression already in the lateral epithelial somite where its expression is maximal (n = 8; Fig. 5 and Fig. 6 B), confirming that BMP is required early during endothelial development.

Bottom Line: Notch activity is necessary for smooth muscle production while inhibiting striated muscle differentiation, yet it does not affect initial development of endothelial cells.Hence, although different mechanisms are responsible for smooth muscle and endothelium generation, the choice to become smooth versus striated muscle depends on a single signaling system.Altogether, these findings underscore the spatial and temporal complexity of lineage diversification in an apparently homogeneous epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

ABSTRACT
We address the mechanisms underlying generation of skeletal muscle, smooth muscle, and endothelium from epithelial progenitors in the dermomyotome. Lineage analysis shows that of all epithelial domains, the lateral region is the most prolific producer of smooth muscle and endothelium. Importantly, individual labeled lateral somitic cells give rise to only endothelial or mural cells (not both), and endothelial and mural cell differentiation is driven by distinct signaling systems. Notch activity is necessary for smooth muscle production while inhibiting striated muscle differentiation, yet it does not affect initial development of endothelial cells. On the other hand, bone morphogenetic protein signaling is required for endothelial cell differentiation and/or migration but inhibits striated muscle differentiation and fails to impact smooth muscle cell production. Hence, although different mechanisms are responsible for smooth muscle and endothelium generation, the choice to become smooth versus striated muscle depends on a single signaling system. Altogether, these findings underscore the spatial and temporal complexity of lineage diversification in an apparently homogeneous epithelium.

Show MeSH
Related in: MedlinePlus