Distinct transcriptomic changes in E14.5 mouse skeletal muscle lacking RYR1 or Cav1.1 converge at E18.5

Area of Science:

• Muscle Physiology
• Developmental Biology
• Molecular Genetics

Background:

• Skeletal muscle contraction relies on coupled Ca2+ channels: 1,4-dihydropyridine receptor (Cav1.1) and type 1 ryanodine receptor (RYR1).
• The roles of Cav1.1 and RYR1 in myogenesis (skeletal muscle development) are not fully understood.

Purpose of the Study:

• To investigate the specific functions of Cav1.1 and RYR1 during skeletal muscle development.
• To analyze histological and transcriptomic changes in RYR1-/- and Cav1.1-/- mice during primary and secondary myogenesis.

Main Methods:

• Histological and immunohistological analysis of murine limb skeletal muscle at embryonic days E14.5 and E18.5.
• Microarray analysis to identify differentially regulated genes (DEGs) in WT, RYR1-/-, and Cav1.1-/- mice.
• Gene enrichment analysis to identify affected biological processes and pathways.

Main Results:

• Mutant mice showed progressive histological alterations and increased apoptosis (Cav1.1-/- at E14.5).
• Transcriptomic analysis revealed significant genotype-specific DEGs, with overlap in muscle contraction pathways at E18.5.
• Distinct DEGs related to neuronal/bone development (RYR1-/-) and lipid metabolism (Cav1.1-/-) were identified.

Conclusions:

• Cav1.1 and RYR1 exhibit distinct roles in skeletal muscle primary and secondary myogenesis.
• These findings highlight specific functional contributions of these Ca2+ channels to muscle development and regulation.
• The study provides insights into the molecular mechanisms governing myogenesis and muscle function.