Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca2+ release channel
| Autor: | Anna M. Walter, Nina F. Linde, Gabriele Pfitzer, Jürgen Hescheler, Dilyana Filipova, Martina Deckert, Symeon Papadopoulos, Mostafa A. Ardestani, John Antonydas Gaspar, Agapios Sachinidis, Anna Brunn |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RYR1 medicine.medical_specialty Multidisciplinary Ryanodine receptor Muscle organ Skeletal muscle Biology MyoD musculoskeletal system Article 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Endocrinology Internal medicine medicine Signal transduction Transcription factor tissues Calcium signaling |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | In mature skeletal muscle, the intracellular Ca2+ concentration rises dramatically upon membrane depolarization, constituting the link between excitation and contraction. This process requires Ca2+ release from the sarcoplasmic reticulum via the type 1 ryanodine receptor (RYR1). However, RYR1’s potential roles in muscle development remain obscure. We used an established RyR1- null mouse model, dyspedic, to investigate the effects of the absence of a functional RYR1 and, consequently, the lack of RyR1-mediated Ca2+ signaling, during embryogenesis. Homozygous dyspedic mice die after birth and display small limbs and abnormal skeletal muscle organization. Skeletal muscles from front and hind limbs of dyspedic fetuses (day E18.5) were subjected to microarray analyses, revealing 318 differentially expressed genes. We observed altered expression of multiple transcription factors and members of key signaling pathways. Differential regulation was also observed for genes encoding contractile as well as muscle-specific structural proteins. Additional qRT-PCR analysis revealed altered mRNA levels of the canonical muscle regulatory factors Six1, Six4, Pax7, MyoD, MyoG and MRF4 in mutant muscle, which is in line with the severe developmental retardation seen in dyspedic muscle histology analyses. Taken together, these findings suggest an important non-contractile role of RyR1 or RYR1-mediated Ca2+ signaling during muscle organ development. |
| Databáze: | OpenAIRE |
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