Universität zu Köln

Filipova, Dilyana ORCID: 0000-0003-3532-9765, Walter, Anna M., Gaspar, John A., Brunn, Anna, Linde, Nina F., Ardestani, Mostafa A., Deckert, Martina, Hescheler, Juergen, Pfitzer, Gabriele, Sachinidis, Agapios and Papadopoulos, Symeon (2016). Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca2+ release channel. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Filipova, Dilyana UNSPECIFIED orcid.org/0000-0003-3532-9765 UNSPECIFIED Walter, Anna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaspar, John A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunn, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Linde, Nina F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ardestani, Mostafa A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfitzer, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulos, Symeon UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-285887
DOI:	10.1038/srep20050
Journal or Publication Title:	Sci Rep
Volume:	6
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACTIVATED PROTEIN-KINASES; CALCIUM TRANSIENTS; INTRACELLULAR CA2+; EXPRESSION; DENERVATION; ADAPTATION; MUTATIONS; REGULATOR; TENASCIN; MYOTUBES Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28588