Perimysial Fibroblasts of Extraocular Muscle, as Unique as the Muscle Fibers

Kusner, Linda L.; Young, Andrew; Tjoe, Steven; Leahy, Patrick; Kaminski, Henry J.

doi:10.1167/iovs.08-2857

Cited by 23 publications

(19 citation statements)

References 55 publications

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“…In particular, we found in vitro that myoblasts cultured in the presence of Tcf4 + fibroblasts formed larger, more multinucleated myofibers than myoblasts cultured alone (Mathew et al, 2011). In addition, other experiments have shown in vitro that fibroblasts are a source of trophic signals for myogenic cells (Cooper et al, 2004;Joe et al, 2010;Kusner et al, 2010;Melone et al, 2000). However, this is the first demonstration in vivo that fibroblasts regulate muscle regeneration.…”

Section: Pax7mentioning

confidence: 58%

Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

et al. 2011

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SUMMARYMuscle regeneration requires the coordinated interaction of multiple cell types. Satellite cells have been implicated as the primary stem cell responsible for regenerating muscle, yet the necessity of these cells for regeneration has not been tested. Connective tissue fibroblasts also are likely to play a role in regeneration, as connective tissue fibrosis is a hallmark of regenerating muscle. However, the lack of molecular markers for these fibroblasts has precluded an investigation of their role. Using Tcf4, a newly identified fibroblast marker, and Pax7, a satellite cell marker, we found that after injury satellite cells and fibroblasts rapidly proliferate in close proximity to one another. To test the role of satellite cells and fibroblasts in muscle regeneration in vivo, we created Pax7CreERT2 and Tcf4 CreERT2 mice and crossed these to R26R DTA mice to genetically ablate satellite cells and fibroblasts. Ablation of satellite cells resulted in a complete loss of regenerated muscle, as well as misregulation of fibroblasts and a dramatic increase in connective tissue. Ablation of fibroblasts altered the dynamics of satellite cells, leading to premature satellite cell differentiation, depletion of the early pool of satellite cells, and smaller regenerated myofibers. Thus, we provide direct, genetic evidence that satellite cells are required for muscle regeneration and also identify resident fibroblasts as a novel and vital component of the niche regulating satellite cell expansion during regeneration. Furthermore, we demonstrate that reciprocal interactions between fibroblasts and satellite cells contribute significantly to efficient, effective muscle regeneration.

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Section: Pax7mentioning

confidence: 58%

Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

et al. 2011

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“…Innervation and thyroid hormones have been identified as important extrinsic regulators of fiber type development (Schiaffino and Reggiani, 1996). In addition, previous in vitro studies and avian surgical manipulations had hinted that the connective tissue might modulate fiber type (Cooper et al, 2004;Kusner et al, 2010;Robson et al, 1994), but the role of connective tissue has never been rigorously established by loss-of-function or in vivo experiments.…”

Section: Tcf4 Is a Marker Of Muscle Connective Tissue Fibroblasts Andmentioning

confidence: 99%

“…Interestingly, classic quail-chick chimera studies had hinted that lateral-plated derived tissue (which includes the connective tissue) might regulate the rate of muscle maturation during development (Armand et al, 1983). Also, several in vitro studies (Cooper et al, 2004;Joe et al, 2010;Kusner et al, 2010;Melone et al, 2000;Quinn et al, 1990) show that postnatal fibroblasts are a source of secreted trophic signals for myogenic cells. Recently, the molecular nature of some of these postnatal fibroblast signals has begun to be revealed.…”

Section: Research Articlementioning

confidence: 99%

Connective tissue fibroblasts and Tcf4 regulate myogenesis

et al. 2011

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SUMMARYMuscle and its connective tissue are intimately linked in the embryo and in the adult, suggesting that interactions between these tissues are crucial for their development. However, the study of muscle connective tissue has been hindered by the lack of molecular markers and genetic reagents to label connective tissue fibroblasts. Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4GFPCre mice allow genetic manipulation of these fibroblasts. Using this new reagent, we find that connective tissue fibroblasts critically regulate two aspects of myogenesis: muscle fiber type development and maturation. Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating the expression of slow myosin heavy chain. Also, fibroblasts promote the switch from fetal to adult muscle by repressing (via Tcf4-dependent signals) the expression of developmental embryonic myosin and promoting (via a Tcf4-independent mechanism) the formation of large multinucleate myofibers. In addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of intrinsic regulation of muscle fiber type development. Unlike other intrinsic regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow and fast myogenesis, thereby promoting overall maturation of muscle fiber type. Thus, we have identified novel extrinsic and intrinsic mechanisms regulating myogenesis. Most significantly, our data demonstrate for the first time that connective tissue is important not only for adult muscle structure and function, but is a vital component of the niche within which muscle progenitors reside and is a critical regulator of myogenesis.

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“…43 Recent studies suggest that fibroblasts in EOM differ from those in limb muscles. 44 It may be that the injured tendon releases signaling factors that play a role in EOM adaptations after recession and tenotomy surgery. Hindlimb suspension studies support this notion as, after unloading, both insulin growth factor-I and mechanogrowth factor increase in the muscle tendons.…”

Section: Eom Tendonsmentioning

confidence: 99%

Effects of Recession versus Tenotomy Surgery without Recession in Adult Rabbit Extraocular Muscle

Christiansen

Antunes-Foschini

McLoon

2010

Invest. Ophthalmol. Vis. Sci.

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Perimysial Fibroblasts of Extraocular Muscle, as Unique as the Muscle Fibers

Abstract: Fibroblasts from EOM demonstrate distinct properties that distinguish them from leg muscle-derived fibroblasts. The distinct properties of EOM-Fibro may support the unique EOM phenotype and contribute to their differential involvement in disease.

Cited by 23 publications

References 55 publications

Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

Connective tissue fibroblasts and Tcf4 regulate myogenesis

Effects of Recession versus Tenotomy Surgery without Recession in Adult Rabbit Extraocular Muscle

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