Molecular regulation of high muscle mass in developing Blonde d’Aquitaine cattle fetuses Isabelle Cassar-Malek, Céline Boby, Brigitte Picard, Antonio Reverter-Gomez, Nicholas Hudson To cite this version: Isabelle Cassar-Malek, Céline Boby, Brigitte Picard, Antonio Reverter-Gomez, Nicholas Hudson. Molecular regulation of high muscle mass in developing Blonde d’Aquitaine cattle fetuses. Biology Open, Royal Society, 2017, 6 (10), pp.bio.024950. 10.1242/bio.024950. hal-01607200 HAL Id: hal-01607200 https://hal.archives-ouvertes.fr/hal-01607200 Submitted on 26 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License © 2017. Published by The Company of Biologists Ltd | Biology Open (2017) 6, 1483-1492 doi:10.1242/bio.024950 RESEARCH ARTICLE Molecular regulation of high muscle mass in developing Blonde d’Aquitaine cattle foetuses Isabelle Cassar-Malek1,Céline Boby1, Brigitte Picard1, Antonio Reverter2 and Nicholas J. Hudson3,* ABSTRACT scientists have numerous breeds at their disposal that, through The Blonde d’Aquitaine (BA) is a French cattle breed with enhanced generations of selective breeding, possess strong phenotypes muscularity, partly attributable to a MSTN mutation. The BA expressed against a relatively stable background genome. The m. Semitendinosus has a faster muscle fibre isoform phenotype mechanistic basis of feed efficiency is not known, but variation in comprising a higher proportion of fast type IIX fibres compared to age- feed intake, digestion, metabolism, activity and thermogenesis have matched Charolais (CH). To better understand the molecular network all been implicated (Herd and Arthur, 2009). Focussing on skeletal of modifications in BA compared to CH muscle, we assayed the muscle tissue, mammals possess a range of fibre types with different transcriptomes of the m. Semitendinosus at 110, 180, 210 and functional properties. Interestingly, we already know that highly 260 days postconception (dpc). We used a combination of differential feed-efficient breeds of all the major production species, such as expression (DE) and regulatory impact factors (RIF) to compare and Piedmontese cattle (Lehnert et al., 2007), Belgian Blue cattle contrast muscle gene expression between the breeds. Prominently (Bouley et al., 2005; Deveaux et al., 2001; Hanset et al., 1987), developmentally regulated genes in both breeds reflected the Large White pigs (Lefaucheur and Ecolan, 2005; Lefaucheur et al., replacement of embryonic myosin isoforms (MYL4, MYH3)withadult 2004, 2011), German Landrace pigs (Rehfeldt et al., 2008) and isoforms (MYH1) and the upregulation of mitochondrial metabolism Callipyge sheep (Jackson et al., 1997a,b,c), collectively possess (CKMT2, AGXT2L1) in preparation for birth. However, the transition to exactly the same shift towards a whiter type IIB/IIX phenotype a fast, glycolytic muscle phenotype in the MSTN mutant BA is compared to their wild counterparts and less efficient breeds. detectable through downregulation of various slow twitch subunits Broiler chicken muscle can be seen as the most extreme example of (TNNC1, MYH7, TPM3, CSRP3) beyond 210 dpc, and a small but this phenotype (Kiessling, 1977). consistent genome-wide reduction in mRNA encoding the A bioenergetic feature of type IIB/X fibres is a lower mitoproteome. Across the breeds, NRIP2 is the regulatory gene mitochondrial content than type I and IIA. This implies that the possessing a network change most similar to that of MSTN. glycolytic fibre shift documented above will result in muscle tissue mitochondrial content decreasing. Direct measures of mitochondrial KEY WORDS: Skeletal muscle, Myostatin, Mitochondria, Genomics, content have not been routinely taken. However, Vincent et al. Myogenesis (2015) recently discovered that when divergently selecting on residual feed intake, the more efficient pigs possessed a lower BACKGROUND muscle oxidative metabolism and mitochondrial content. Similarly, Feed is the single largest cost in many intensive livestock farming in Yorkshire boars, low muscle mitochondrial content has recently enterprises including beef feedlotting (Robinson and Oddy, 2004). been associated with higher feed efficiency (Fu et al., 2017). In Consequently, the food production industry is interested in addition, double-muscled cattle or cattle selected for high growth enhancing the feed conversion efficiency of its major production potential and feed efficiency also possess less oxidative muscles species. Accelerating improvements in these areas beyond what can (Sudre et al., 2005; Picard et al., 2006), as do Charolais (CH) be achieved by traditional artificial selection on phenotype first divergent for muscle mass (Sudre et al., 2005). A reduction in requires a base level of understanding. What physiological and oxidative capacity has previously been argued to improve metabolic developmental processes are taking place, and what are their efficiency on the grounds that it is inefficient to possess too much fuel functional limits? Fortunately, domesticated species provide burning capacity (Hudson, 2009). The engineering argument runs as opportunity to uncover the molecular mechanisms underpinning follows: it is not economical to pay for the construction (biogenesis), phenotypes of interest (Andersson and Georges, 2004). Agricultural maintenance (trans-membrane proton gradient) and load (space that could be occupied by other cellular structures) of energetically expensive mitochondrial capacity that is not needed. Further, Bottje 1UMR1213 Herbivores, Institut National de la Recherche Agronomique, VetAgro and Carstens (2009) have reviewed the impact of isolated Sup, 63122 Saint Genes̀ Champanelle, Clermont-Ferrand F-63122, France. mitochondrial performance and its impact on poultry and livestock 2Agriculture, Commonwealth Science and Industrial Research Organisation, Queensland Bioscience Precinct, St. Lucia, Brisbane 4075, Australia. 3School of feed, efficiency documenting associations in several species and Agriculture and Food Sciences, University of Queensland, Brisbane 4075, circumstances. These lines of evidence support a role for Australia. mitochondrial function in contributing to variation in feed efficiency. *Author for correspondence ([email protected]) However, the genetic bases of the ‘whitening’ of livestock muscle and other biological aspects of efficiency remain a mystery. Other N.J.H., 0000-0002-3549-9396 than some progress in identifying causal mutations such as the This is an Open Access article distributed under the terms of the Creative Commons Attribution various myostatin (MSTN) mutants, the detailed rewiring of License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. gene regulatory networks that manifest these anatomical and physiological changes through muscle development are largely Received 19 February 2017; Accepted 21 August 2017 unknown. Here, we attempt to shed more light on this question by Biology Open 1483 Downloaded from http://bio.biologists.org/ by guest on June 21, 2018 RESEARCH ARTICLE Biology Open (2017) 6, 1483-1492 doi:10.1242/bio.024950 contrasting the genome-wide muscle transcriptomes of two breeds treatments, we were left with a refined list containing 19,100 probes of cattle. A MSTN mutation has been identified in the Blonde mapping to 10,138 genes. When comparing the breeds for patterns d’Aquitaine (BA) breed (Bouyer et al., 2014) that culminates in of high developmental regulation (including but not limited to greater muscle mass and feed efficiency than the comparison CH, stepwise increases and decreases across development), a number of but not all individuals carry the mutation. In line with the other genes were identified. This was achieved by computing the standard examples given above, BA also has a more glycolytic, less oxidative deviation of expression values across the four time points on a muscle metabolism and a higher proportion of fast glycolytic IIX breed-specific basis. High standard deviations reflect high fibres (Listrat et al., 2001; Picard and Cassar-Malek, 2009). We developmental regulation. The replacement of embryonic myosin analysed m. Semitendinosus samples at three prenatal time points heavy chain isoforms (MYL4, MYH3) with adult isoforms (MYH1) coincident with secondary myogenesis (110 days postconception was observed. Further, we detected an upregulation of creatine (dpc), onset of functional differentiation (180 dpc), completion of kinase (CKMT2), a marker of mitochondrial metabolism, in functional differentiation (210 dpc), in addition to a later time point preparation for birth (Table 1). We also detected strong prior to birth when mature muscle has been established (260 dpc). developmental regulation of an unannotated Open Reading Frame Through the application of several methods including a differential (ORF), C13H20ORF194. AGXT2L1 also has high developmental