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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
A simplified model for lineage segregation in the lateral somite/DM. Endothelial (E), smooth muscle (M), and striated muscle (StM) lineages arise from a common progenitor (Esner et al., 2006). Direct lineage analysis of lateral somite and DM show that fate-restricted progenitors are already detected at the epithelial somite stage. Of the three lineages, endothelial cells constitute a population of early segregated progenitors whose differentiation and/or migration depends on lateral mesoderm-derived BMP. In turn, we postulate the existence of a common intermediate progenitor for smooth and striated muscle sublineages from which separate fates are generated over a more extended period. The segregation of these fates is a binary choice that depends on Notch signaling. Elevated activity of Notch stimulates smooth muscle development, whereas lower levels or inhibition of Notch signaling drive generation of striated muscle. Under experimental conditions, abrogation of Notch function by overexpression of Numb results in myofiber differentiation in the myotome at the expense of mitotic muscle progenitors (satellite cell or myofiber progenitors). It is possible, however, that in the embryo, more subtle differences in levels of Notch activity modulate the balance between generating a myofiber or remaining a mitotic muscle precursor within the striated muscle sublineage. Likewise, inhibition of BMP activity was found to stimulate premature MyoD transcription and lateral myofiber differentiation (Kahane et al., 2007) leading to a reduction in cell number within myotomes (Fig. 6). Hence, the development of striated muscle precursors is negatively modulated by Notch as well as by BMP signaling cascades. Phenotypic segregation in the DM, therefore, exemplifies how two signaling cascades produce three distinct lineages by combining agonistic and antagonistic interactions.
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fig7: A simplified model for lineage segregation in the lateral somite/DM. Endothelial (E), smooth muscle (M), and striated muscle (StM) lineages arise from a common progenitor (Esner et al., 2006). Direct lineage analysis of lateral somite and DM show that fate-restricted progenitors are already detected at the epithelial somite stage. Of the three lineages, endothelial cells constitute a population of early segregated progenitors whose differentiation and/or migration depends on lateral mesoderm-derived BMP. In turn, we postulate the existence of a common intermediate progenitor for smooth and striated muscle sublineages from which separate fates are generated over a more extended period. The segregation of these fates is a binary choice that depends on Notch signaling. Elevated activity of Notch stimulates smooth muscle development, whereas lower levels or inhibition of Notch signaling drive generation of striated muscle. Under experimental conditions, abrogation of Notch function by overexpression of Numb results in myofiber differentiation in the myotome at the expense of mitotic muscle progenitors (satellite cell or myofiber progenitors). It is possible, however, that in the embryo, more subtle differences in levels of Notch activity modulate the balance between generating a myofiber or remaining a mitotic muscle precursor within the striated muscle sublineage. Likewise, inhibition of BMP activity was found to stimulate premature MyoD transcription and lateral myofiber differentiation (Kahane et al., 2007) leading to a reduction in cell number within myotomes (Fig. 6). Hence, the development of striated muscle precursors is negatively modulated by Notch as well as by BMP signaling cascades. Phenotypic segregation in the DM, therefore, exemplifies how two signaling cascades produce three distinct lineages by combining agonistic and antagonistic interactions.

Mentions: The second part of this study demonstrates that Notch signaling plays a physiological role in the generation of smooth versus striated muscle from the lateral DM and has little if any effect on initial specification of the endothelium. Reciprocally, BMP signaling, despite its effect on the differentiation and/or migration of somite-derived endothelial cells via regulation of VEGFr2 expression, does not seem to affect smooth muscle development yet inhibits differentiation of myotomal myofibers (Pourquie et al., 1996). Thus, we suggest that initial development of mural and endothelial cells is governed by different mechanisms. In contrast, development of mural and striated muscle sublineages is a binary choice that depends upon a single signaling system (Fig. 7).


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)

A simplified model for lineage segregation in the lateral somite/DM. Endothelial (E), smooth muscle (M), and striated muscle (StM) lineages arise from a common progenitor (Esner et al., 2006). Direct lineage analysis of lateral somite and DM show that fate-restricted progenitors are already detected at the epithelial somite stage. Of the three lineages, endothelial cells constitute a population of early segregated progenitors whose differentiation and/or migration depends on lateral mesoderm-derived BMP. In turn, we postulate the existence of a common intermediate progenitor for smooth and striated muscle sublineages from which separate fates are generated over a more extended period. The segregation of these fates is a binary choice that depends on Notch signaling. Elevated activity of Notch stimulates smooth muscle development, whereas lower levels or inhibition of Notch signaling drive generation of striated muscle. Under experimental conditions, abrogation of Notch function by overexpression of Numb results in myofiber differentiation in the myotome at the expense of mitotic muscle progenitors (satellite cell or myofiber progenitors). It is possible, however, that in the embryo, more subtle differences in levels of Notch activity modulate the balance between generating a myofiber or remaining a mitotic muscle precursor within the striated muscle sublineage. Likewise, inhibition of BMP activity was found to stimulate premature MyoD transcription and lateral myofiber differentiation (Kahane et al., 2007) leading to a reduction in cell number within myotomes (Fig. 6). Hence, the development of striated muscle precursors is negatively modulated by Notch as well as by BMP signaling cascades. Phenotypic segregation in the DM, therefore, exemplifies how two signaling cascades produce three distinct lineages by combining agonistic and antagonistic interactions.
© Copyright Policy
Related In: Results  -  Collection

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fig7: A simplified model for lineage segregation in the lateral somite/DM. Endothelial (E), smooth muscle (M), and striated muscle (StM) lineages arise from a common progenitor (Esner et al., 2006). Direct lineage analysis of lateral somite and DM show that fate-restricted progenitors are already detected at the epithelial somite stage. Of the three lineages, endothelial cells constitute a population of early segregated progenitors whose differentiation and/or migration depends on lateral mesoderm-derived BMP. In turn, we postulate the existence of a common intermediate progenitor for smooth and striated muscle sublineages from which separate fates are generated over a more extended period. The segregation of these fates is a binary choice that depends on Notch signaling. Elevated activity of Notch stimulates smooth muscle development, whereas lower levels or inhibition of Notch signaling drive generation of striated muscle. Under experimental conditions, abrogation of Notch function by overexpression of Numb results in myofiber differentiation in the myotome at the expense of mitotic muscle progenitors (satellite cell or myofiber progenitors). It is possible, however, that in the embryo, more subtle differences in levels of Notch activity modulate the balance between generating a myofiber or remaining a mitotic muscle precursor within the striated muscle sublineage. Likewise, inhibition of BMP activity was found to stimulate premature MyoD transcription and lateral myofiber differentiation (Kahane et al., 2007) leading to a reduction in cell number within myotomes (Fig. 6). Hence, the development of striated muscle precursors is negatively modulated by Notch as well as by BMP signaling cascades. Phenotypic segregation in the DM, therefore, exemplifies how two signaling cascades produce three distinct lineages by combining agonistic and antagonistic interactions.
Mentions: The second part of this study demonstrates that Notch signaling plays a physiological role in the generation of smooth versus striated muscle from the lateral DM and has little if any effect on initial specification of the endothelium. Reciprocally, BMP signaling, despite its effect on the differentiation and/or migration of somite-derived endothelial cells via regulation of VEGFr2 expression, does not seem to affect smooth muscle development yet inhibits differentiation of myotomal myofibers (Pourquie et al., 1996). Thus, we suggest that initial development of mural and endothelial cells is governed by different mechanisms. In contrast, development of mural and striated muscle sublineages is a binary choice that depends upon a single signaling system (Fig. 7).

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