Molecular regulation of enhanced muscle mass in developing Blond Aquitaine foetuses compared to Charolais

ABSTRACT: Background : The Blonde Aquitaine (BA) is a French beef breed with enhanced muscularity of unknown genetic origin. Targeted sequencing has shown that the BA is not a carrier of any of the bovine MSTN mutations. At the protein level the BA shows a transition to a faster muscle isoform phenotype with a greater proportion of type IIX and a smaller proportion of type I fibres than comparison Charolais (CH). Associated modifications in the activity of oxidative and glycolytic enzymes were also previously detected. Collectively, these changes are often observed in breeds of production species selected for enhanced growth and efficiency, but the underlying molecular mechanisms are unknown. Method : We examined the transcriptome of the Longissimus thoracis muscle at 4 gestational stages (110, 180, 210, and 260 dpc) in BA and CH foetuses. These time points coincide with primary and secondary myogenesis and functional differentiation. Total RNA was hybridised to the Agilent one-colour microarray platform containing 45,220 probes mapped to 17646 protein coding bovine genes. Following normalisation, we used a combination of differential expression (limma method, Smyth & al 2005) and a network theory method based on differential co-expression analysis (Hudson & al 2009) to compare and contrast the two muscle transcriptomes. Conclusions : In both breeds the most developmentally-regulated genes included: embryonic muscle subunit isoforms (e.g. MYL4) whose expression dropped dramatically prior to birth when they are replaced by the adult isoforms; metabolic enzymes (e.g. the mitochondrially-localised sarcomeric creatine kinase CKMT2) that prepare the foetus for functional independence postpartum, and 1 probe out of 4 representing a gene of unknown function (C13H20ORF194) also previously published as highly developmentally regulated in Wagyu by Hereford longissimus muscle (Hudson & al 2013). In contrasting the breeds, MSTN was the 2nd most differentially expressed muscle gene between the breeds, being approximately 4-fold down-regulated in CH at each of the time points. Given MSTN is a growth inhibitor, this result may reflect either divergent muscle mass or fibre composition in foetuses and could account for the low muscle development of BA calves at birth. Among the most differentially connected transcriptional regulators we prioritised expected molecules like MSTN, but also unexpected ones like PROX1, NMI, MBD1, NRIP2 and TAF12. Although not differentially expressed at the transcript level these molecules are transcriptionally rewired between the breeds and may form attractive new candidates for the development of differential muscle mass and fibre composition in cattle.

ORGANISM(S): Bos taurus

PROVIDER: GSE60844 | GEO | 2015/08/01

SECONDARY ACCESSION(S): PRJNA259655

REPOSITORIES: GEO