Muscle stem cells and model systems for their investigation

Figeac, Nicolas; Daczewska, Małgorzata; Marcelle, Christophe; Jagla, Krzysztof

doi:10.1002/dvdy.21345

Cited by 51 publications

(32 citation statements)

References 105 publications

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“…The AMPs have the capacity for self-renewal and are not committed to a particular muscle lineage, characteristics similar to those of mammalian muscle satellite cells (Figeac et al, 2007). The genes regulated by the combination of Twi and Notch might therefore be important for maintaining these cells as progenitors with myogenic potential.…”

Section: What Are the Likely Characteristics Conferred On Cells By Thmentioning

confidence: 99%

Specificity of Notch pathway activation: Twist controls the transcriptional output in adult muscle progenitors

et al. 2010

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SUMMARYCell-cell signalling mediated by Notch regulates many different developmental and physiological processes and is involved in a variety of human diseases. Activation of Notch impinges directly on gene expression through the Suppressor of Hairless [Su(H)] DNA-binding protein. A major question that remains to be elucidated is how the same Notch signalling pathway can result in different transcriptional responses depending on the cellular context and environment. Here, we have investigated the factors required to confer this specific response in Drosophila adult myogenic progenitor-related cells. Our analysis identifies Twist (Twi) as a crucial co-operating factor. Enhancers from several direct Notch targets require a combination of Twi and Notch activities for expression in vivo; neither alone is sufficient. Twi is bound at target enhancers prior to Notch activation and enhances Su(H) binding to these regulatory regions. To determine the breadth of the combinatorial regulation we mapped Twi occupancy genome-wide in DmD8 myogenic progenitor-related cells by chromatin immunoprecipitation. Comparing the sites bound by Su(H) and by Twi in these cells revealed a strong association, identifying a large spectrum of co-regulated genes. We conclude that Twi is an essential Notch co-regulator in myogenic progenitor cells and has the potential to confer specificity on Notch signalling at over 170 genes, showing that a single factor can have a profound effect on the output of the pathway.

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Section: What Are the Likely Characteristics Conferred On Cells By Thmentioning

confidence: 99%

Specificity of Notch pathway activation: Twist controls the transcriptional output in adult muscle progenitors

et al. 2010

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“…In the case of muscle progenitors, these asymmetric divisions typically generate two distinct muscle founder cells that go on to form two different larval muscle fibers. In some instances, one sibling of a muscle founder cell gives rise to certain heart precursors or to a stem cell-like adult muscle progenitor that will contribute to the adult body wall musculature (reviewed by Figeac et al, 2007;Speicher et al, 2008). Subsequently, muscle founder myoblasts fuse with surrounding fusion-competent myoblasts to form distinct body wall muscle fibers.…”

Section: Introductionmentioning

confidence: 99%

Org-1, the Drosophila ortholog of Tbx1, is a direct activator of known identity genes during muscle specification

et al. 2012

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SUMMARYMembers of the T-Box gene family of transcription factors are important players in regulatory circuits that generate myogenic and cardiogenic lineage diversities in vertebrates. We show that during somatic myogenesis in Drosophila, the single ortholog of vertebrate Tbx1, optomotor-blind-related-gene-1 (org-1), is expressed in a small subset of muscle progenitors, founder cells and adult muscle precursors, where it overlaps with the products of the muscle identity genes ladybird (lb) and slouch (slou). In addition, org-1 is expressed in the lineage of the heart-associated alary muscles. org-1 null mutant embryos lack Lb and Slou expression within the muscle lineages that normally co-express org-1. As a consequence, the respective muscle fibers and adult muscle precursors are either severely malformed or missing, as are the alary muscles. To address the mechanisms that mediate these regulatory interactions between Org-1, Lb and Slou, we characterized distinct enhancers associated with somatic muscle expression of lb and slou. We demonstrate that these lineage-and stage-specific cis-regulatory modules (CRMs) bind Org-1 in vivo, respond to org-1 genetically and require T-box domain binding sites for their activation. In summary, we propose that org-1 is a common and direct upstream regulator of slou and lb in the developmental pathway of these two neighboring muscle lineages. Cross-repression between slou and lb and combinatorial activation of lineage-specific targets by Org-1-Slou and Org-1-Lb, respectively, then leads to the distinction between the two lineages. These findings provide new insights into the regulatory circuits that control the proper pattering of the larval somatic musculature in Drosophila.

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“…For example, transient populations of neural stem cells called neuroblasts undergo a series of asymmetric cell divisions that ensure self-renewal and at the same time give rise to a large range of neural lineages that undergo differentiation (Yu et al, 2006). In the embryonic mesoderm, muscle progenitor cells were shown to divide asymmetrically like the neuroblasts (Ruiz Gomez et al, 1997), but unlike neuroblasts, they divide only once, and give rise either to two distinct muscle founder cells that enter the differentiation process or to a muscle founder and a cell called an adult muscle precursor (AMP) that keeps an undifferentiated state (Ruiz Gomez et al, 1997;Figeac et al, 2007). As the AMPs express markers specific to muscle progenitors, such as the b-HLH transcription factor Twist (Bate et al, 1991;Figeac et al, 2007), the asymmetric cell division leading to the production of an AMP resembles the asymmetric cell division of the neuroblasts that ensure self-renewal.…”

Section: Introductionmentioning

confidence: 99%

Drosophila adult muscle precursors form a network of interconnected cells and are specified by the rhomboid-triggered EGF pathway

et al. 2010

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SUMMARYIn Drosophila, a population of muscle-committed stem-like cells called adult muscle precursors (AMPs) keeps an undifferentiated and quiescent state during embryonic life. The embryonic AMPs are at the origin of all adult fly muscles and, as we demonstrate here, they express repressors of myogenic differentiation and targets of the Notch pathway known to be involved in muscle cell stemness. By targeting GFP to the AMP cell membranes, we show that AMPs are tightly associated with the peripheral nervous system and with a subset of differentiated muscles. They send long cellular processes running along the peripheral nerves and, by the end of embryogenesis, form a network of interconnected cells. Based on evidence from laser ablation experiments, the main role of these cellular extensions is to maintain correct spatial positioning of AMPs. To gain insights into mechanisms that lead to AMP cell specification, we performed a gain-of-function screen with a special focus on lateral AMPs expressing the homeobox gene ladybird. Our data show that the rhomboid-triggered EGF signalling pathway controls both the specification and the subsequent maintenance of AMP cells. This finding is supported by the identification of EGF-secreting cells in the lateral domain and the EGF-dependent regulatory modules that drive expression of the ladybird gene in lateral AMPs. Taken together, our results reveal an unsuspected capacity of embryonic AMPs to form a cell network, and shed light on the mechanisms governing their specification and maintenance.

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Muscle stem cells and model systems for their investigation

Cited by 51 publications

References 105 publications

Specificity of Notch pathway activation: Twist controls the transcriptional output in adult muscle progenitors

Specificity of Notch pathway activation: Twist controls the transcriptional output in adult muscle progenitors

Org-1, the Drosophila ortholog of Tbx1, is a direct activator of known identity genes during muscle specification

Drosophila adult muscle precursors form a network of interconnected cells and are specified by the rhomboid-triggered EGF pathway

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