Effects of retinoic acid signaling on extraocular muscle myogenic precursor cells in vitro

Hebert, Sadie L.; Fitzpatrick, Krysta R.; McConnell, Samantha A; Cucak, Anja; Yuan, Ching; McLoon, Linda K.

doi:10.1016/j.yexcr.2017.10.007

Cited by 7 publications

(4 citation statements)

References 44 publications

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“…Exogenous RA (bead implantation) in chick embryos impacts the expression of the myogenic markers Pitx2 and Tbx1 (Bothe et al, 2011). Furthermore, Retinoid X receptor (RXR) co-localizes with PITX2 in extraocular muscle cells (Hebert et al, 2017). Together with our results, this clearly shows that perturbed RA signaling results in downregulation of Pitx2 in BA1 and BA2, which in turn results in branchiomeric muscle defects.…”

Section: Diverse Reactions Of Muscle Precursor Cells To Ra Signalingsupporting

confidence: 73%

Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling

Wang

Miura

et al. 2021

Front. Cell Dev. Biol.

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The first and second branchiomeric (branchial arch) muscles are craniofacial muscles that derive from branchial arch mesoderm. In mammals, this set of muscles is indispensable for jaw movement and facial expression. Defects during embryonic development that result in congenital partial absence of these muscles can have significant impact on patients’ quality of life. However, the detailed molecular and cellular mechanisms that regulate branchiomeric muscle development remains poorly understood. Herein we investigated the role of retinoic acid (RA) signaling in developing branchiomeric muscles using mice as a model. We administered all-trans RA (25 mg/kg body weight) to Institute of Cancer Research (ICR) pregnant mice by gastric intubation from E8.5 to E10.5. In their embryos at E13.5, we found that muscles derived from the first branchial arch (temporalis, masseter) and second branchial arch (frontalis, orbicularis oculi) were severely affected or undetectable, while other craniofacial muscles were hypoplastic. We detected elevated cell death in the branchial arch mesoderm cells in RA-treated embryos, suggesting that excessive RA signaling reduces the survival of precursor cells of branchiomeric muscles, resulting in the development of hypoplastic craniofacial muscles. In order to uncover the signaling pathway(s) underlying this etiology, we focused on Pitx2, Tbx1, and MyoD1, which are critical for cranial muscle development. Noticeably reduced expression of all these genes was detected in the first and second branchial arch of RA-treated embryos. Moreover, elevated RA signaling resulted in a reduction in Dlx5 and Dlx6 expression in cranial neural crest cells (CNCCs), which disturbed their interactions with branchiomeric mesoderm cells. Altogether, we discovered that embryonic craniofacial muscle defects caused by excessive RA signaling were associated with the downregulation of Pitx2, Tbx1, MyoD1, and Dlx5/6, and reduced survival of cranial myogenic precursor cells.

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Section: Diverse Reactions Of Muscle Precursor Cells To Ra Signalingsupporting

confidence: 73%

Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling

Wang

Miura

et al. 2021

Front. Cell Dev. Biol.

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“…Consistently, in the present study, our results demonstrated that administration of bexarotene significantly increased the RXR/PPARγ interaction, and upregulated the expression of SIRT6, while downregulating the pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α at 24 h after SAH. UVI3003, a selective RXR antagonist [32, 47, 48], could ultimately prevent the beneficial effects of RXR activation in retinal degenerations [49]. Similarly, when we inhibited RXR using UVI3003 or knockdown RXR before SAH induction, the effects of bexarotene treatment on PPARγ/SIRT6 upregulation and neuroinflammation suppression as well as neurological deficit improvement were abolished at 24 h after SAH.…”

Section: Discussionmentioning

confidence: 99%

Activation of retinoid X receptor by bexarotene attenuates neuroinflammation via PPARγ/SIRT6/FoxO3a pathway after subarachnoid hemorrhage in rats

Zuo

Huang

Enkhjargal

et al. 2019

J Neuroinflammation

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Background Subarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high mortality and disabilities. Retinoid X receptor (RXR) has been shown to be neuroprotective against ischemia/reperfusion injury. This study aimed to investigate the effects of the selective RXR agonist bexarotene on neuroinflammation in a rat model of SAH. Methods Two hundred male Sprague-Dawley rats were used. The endovascular perforation induced SAH. Bexarotene was administered intraperitoneally at 1 h after SAH induction. To investigate the underlying mechanism, the selective RXR antagonist UVI3003 and RXR siRNA or SIRT6 inhibitor OSS128167 was administered via intracerebroventricular 1 h before SAH induction. Post-SAH assessments including SAH grade, neurological score, brain water content, Western blot, and immunofluorescence were performed. Results The endogenous RXR and sirtuin 6 (SIRT6) protein levels were increased after SAH. Bexarotene treatment significantly reduced brain edema and improved the short-/long-term neurological deficit after SAH. Mechanistically, bexarotene increased the levels of PPARγ and SIRT6; decreased the expression of phosphorylated FoxO3a (p-FoxO3a), IL-6, IL-1β, and TNF-a; and inhibited the microglia activation and neutrophils infiltration at 24 h after SAH. Either UVI3003, OSS128167, or RXR siRNA abolished the neuroprotective effects of bexarotene and its regulation on protein levels of PPARγ/SIRT6/p-FoxO3a after SAH. Conclusions The activation of RXR by bexarotene attenuated neuroinflammation and improved neurological deficits after SAH. The anti-neuroinflammatory effect was at least partially through regulating PPARγ/SIRT6/FoxO3a pathway. Bexarotene may be a promising therapeutic strategy in the management of SAH patients. Electronic supplementary material The online version of this article (10.1186/s12974-019-1432-5) contains supplementary material, which is available to authorized users.

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“…In contrast, mice heterozygous for the Pitx2 null allele and those in which the Pitx2 knockout was limited to NC cells were viable and displayed corneal, iris, and scleral defects similar to ARS in humans ( Chen and Gage, 2016 ). Retinoic acid is a known regulator of Pitx2 expression ( Bohnsack et al, 2012 ; Williams and Bohnsack, 2015 ; Chawla et al, 2016 ; Hebert et al, 2017 ; Draut et al, 2019 ; Williams and Bohnsack, 2019 ), but has differential effects depending on embryonic stage. During the early stages, retinoic acid decreases Pitx2 expression within NC cells migrating toward the pharyngeal arches.…”

Section: Ocular Neural Crest Derivatives: Lessons From Rare Ocular DImentioning

confidence: 99%

The Ocular Neural Crest: Specification, Migration, and Then What?

Williams

Bohnsack

2020

Front. Cell Dev. Biol.

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During vertebrate embryonic development, a population of dorsal neural tube-derived stem cells, termed the neural crest (NC), undergo a series of morphogenetic changes and extensive migration to become a diverse array of cell types. Around the developing eye, this multipotent ocular NC cell population, called the periocular mesenchyme (POM), comprises migratory mesenchymal cells that eventually give rise to many of the elements in the anterior of the eye, such as the cornea, sclera, trabecular meshwork, and iris. Molecular cell biology and genetic analyses of congenital eye diseases have provided important information on the regulation of NC contributions to this area of the eye. Nevertheless, a complete understanding of the NC as a contributor to ocular development remains elusive. In addition, positional information during ocular NC migration and the molecular pathways that regulate end tissue differentiation have yet to be fully elucidated. Further, the clinical challenges of ocular diseases, such as Axenfeld-Rieger syndrome (ARS), Peters anomaly (PA) and primary congenital glaucoma (PCG), strongly suggest the need for better treatments. While several aspects of NC evolution have recently been reviewed, this discussion will consolidate the most recent current knowledge on the specification, migration, and contributions of the NC to ocular development, highlighting the anterior segment and the knowledge obtained from the clinical manifestations of its associated diseases. Ultimately, this knowledge can inform translational discoveries with potential for sorely needed regenerative therapies.

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Effects of retinoic acid signaling on extraocular muscle myogenic precursor cells in vitro

Cited by 7 publications

References 44 publications

Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling

Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling

Activation of retinoid X receptor by bexarotene attenuates neuroinflammation via PPARγ/SIRT6/FoxO3a pathway after subarachnoid hemorrhage in rats

The Ocular Neural Crest: Specification, Migration, and Then What?

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