Sim2 prevents entry into the myogenic program by repressing <i>MyoD</i> transcription during limb embryonic myogenesis

Havis, Emmanuelle; Coumailleau, Pascal; Bonnet, Aline; Bismuth, Keren; Bonnin, Marie-Ange; Johnson, Randy L.; Fan, C.; Relaix, Frédéric; Shi, De Li; Duprez, Delphine

doi:10.1242/dev.072561

Cited by 33 publications

(30 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MyoD is likely to drive MPCs toward terminal differentiation, and, interestingly, its expression in the ventral forelimb was recently reported to be temporally controlled by Sim2 (Havis et al 2012). Consistent with this, a Myogenin-lacZ transgene is not expressed in MyoD À/À limbs, whereas some expression occurs in Myf5 À/À limbs (Kablar et al 2003).…”

Section: Myf5 and Myod May Define Different Myogenic Stages In Limb Mpcsmentioning

confidence: 69%

Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity

et al. 2012

View full text Add to dashboard Cite

How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and populated the prospective muscle masses. Here, we show that Sonic hedgehog (Shh) from the zone of polarizing activity (ZPA) drives myogenesis specifically within the ventral muscle mass. Shh directly induces ventral MPCs to initiate Myf5 transcription and myogenesis through essential Gli-binding sites located in the Myf5 limb enhancer. In the absence of Shh signaling, myogenesis is delayed, MPCs fail to migrate distally, and ventral paw muscles fail to form. Thus, Shh production in the limb ZPA is essential for the spatiotemporal control of myogenesis and coordinates muscle and skeletal development by acting directly to regulate the formation of specific ventral muscles.

show abstract

Section: Myf5 and Myod May Define Different Myogenic Stages In Limb Mpcsmentioning

confidence: 69%

Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity

et al. 2012

View full text Add to dashboard Cite

show abstract

“…In situ hybridization analyses of mouse adult tendons were processed using the mouse Egr1 and Col1a1 digoxigenin-labeled mRNA probes, as previously described for mouse embryos (14,62), followed by nuclear fast red staining. Rat Achilles tendons manipulated with C3H10T1/2-EV or C3H10T1/2-EGR1 cells were fixed in 4% paraformaldehyde, processed for cryostat sections, and stained with H&E. Tendon-like constructs from control C3H10T1/2 or C3H10T1/2-EGR1 cells were fixed in 4% paraformaldehyde, transverse paraffin sectioned, and immunostained with the Ki67 antibody (Ab15580; Abcam) or with the polyclonal antibody against type I collagen (Ab292; Abcam).…”

mentioning

confidence: 99%

“…ChIP assays were performed as previously reported (62). Achilles tendons from 100 postnatal mice were homogenized using a mechanical disruption device (Lysing Matrix A, Fast Prep MP1, 3 × 30 seconds; MP Biomedicals).…”

mentioning

confidence: 99%

Transcription factor EGR1 directs tendon differentiation and promotes tendon repair

Guerquin¹,

Charvet²,

Nourissat³

et al. 2013

J. Clin. Invest.

Self Cite

219

253

View full text Add to dashboard Cite

Tendon formation and repair rely on specific combinations of transcription factors, growth factors, and mechanical parameters that regulate the production and spatial organization of type I collagen. Here, we investigated the function of the zinc finger transcription factor EGR1 in tendon formation, healing, and repair using rodent animal models and mesenchymal stem cells (MSCs). Adult tendons of Egr1 -/-mice displayed a deficiency in the expression of tendon genes, including Scx, Col1a1, and Col1a2, and were mechanically weaker compared with their WT littermates. EGR1 was recruited to the Col1a1 and Col2a1 promoters in postnatal mouse tendons in vivo. Egr1 was required for the normal gene response following tendon injury in a mouse model of Achilles tendon healing. Forced Egr1 expression programmed MSCs toward the tendon lineage and promoted the formation of in vitro-engineered tendons from MSCs. The application of EGR1-producing MSCs increased the formation of tendon-like tissues in a rat model of Achilles tendon injury. We provide evidence that the ability of EGR1 to promote tendon differentiation is partially mediated by TGF-β2. This study demonstrates EGR1 involvement in adult tendon formation, healing, and repair and identifies Egr1 as a putative target in tendon repair strategies.

show abstract

“…Although most bHLH-PAS factors are activators of transcription, Sim2 acts as a transcriptional repressor in mammalian cells (9,35). In addition to its role in CNS development and mental retardation in DS, SIM2 is also involved in muscle and limb development (10,16,21). Recently, several studies have reported that, depending on the origin of tumors, SIM2 may act as a suppressor or stimulator on their growth and development (14,15,28,29).…”

Section: Discussionmentioning

confidence: 99%

SIM2 maintains innate host defense of the small intestine

Chen

Lizaso

Lee

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

The single-minded 2 (SIM2) protein is a basic helix-loop-helix transcription factor regulating central nervous system (CNS) development in Drosophila. In humans, SIM2 is located within the Down syndrome critical region on chromosome 21 and may be involved in the development of mental retardation phenotype in Down syndrome. In this study, knockout of SIM2 expression in mice resulted in a gas distention phenotype in the gastrointestinal tract. We found that SIM2 is required for the expression of all cryptdins and numerous other antimicrobial peptides (AMPs) expressed in the small intestine. The mechanism underlying how SIM2 controls AMP expression involves both direct and indirect regulations. For the cryptdin genes, SIM2 regulates their expression by modulating transcription factor 7-like 2, a crucial regulator in the Wnt/β-catenin signaling pathway, while for other AMP genes, such as RegIIIγ, SIM2 directly activates their promoter activity. Our results establish that SIM2 is a crucial regulator in controlling expression of intestinal AMPs to maintain intestinal innate immunity against microbes.

show abstract

Sim2 prevents entry into the myogenic program by repressing MyoD transcription during limb embryonic myogenesis

Cited by 33 publications

References 56 publications

Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity

Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity

Transcription factor EGR1 directs tendon differentiation and promotes tendon repair

SIM2 maintains innate host defense of the small intestine

Contact Info

Product

Resources

About