Die autosomal-dominant vererbte facioscapulohumerale Muskeldystrophie (FSHD) ist mit einer Prävalenz von etwa 1:20.000 die dritthäufigste Form der hereditären Myopathien. Erste Beschwerden werden meist in der zweiten Lebensdekade beobachtet. Betroffen sind vor allem die Muskulatur von Gesicht, Schultern, Oberarmen, die Fußhebermuskulatur und die Muskeln des Hüftgürtels. FSHD wird durch einen Gendefekt ausgelöst, der den langen Arm des Chromosoms vier (4q35) betrifft, wobei es zur teilweisen Deletion des polymorphen Abschnitts D4Z4, der für das Protein DUX4 codiert, kommt. Dabei treten unter anderem Störungen in der DUX4-Expression, Veränderungen der myogenen Genexpression, eine Unterdrückung der Muskelzelldifferenzierung und eine Inhibition der Muskelbildung auf. FSHD und eine andere Form der Muskeldystrophie, die Emery-Dreifuss-Muskeldystrophie (EDMD), zeigen trotz unterschiedlicher genetischer Ursachen phänotypisch Ähnlichkeiten in der Ausprägung der Erkrankungen. In früheren Studien zeigte die Kernhülle von EDMD-Myoblasten morphologische Auffälligkeiten. In anderen Untersuchungen waren morphologische Veränderungen der Mitochondrien von FSHD-Patienten festzustellen. Daher wurden elektronenmikroskopische Untersuchungen der Kernhülle und der Mitochondrien von FSHD-Myoblasten durchgeführt und mit der entsprechenden Kontrolle verglichen. Hierfür wurden drei verschiedene Zelllinien-Paare in unterschiedlichen Passagen, das heißt unterschiedlicher Anzahl an Subkultivierungen, eingesetzt, wobei in den höheren Passagen vermehrt morphologische Atypien beobachtet werden konnten. Die eingesetzten Zelllinien differenzieren sich durch verschiedene Parameter wie beispielsweise Alter und Geschlecht der Patienten. Dabei zeigten sich sowohl zwischen den Kontrollzellen als auch zwischen den FSHD-Myoblasten Unterschiede. Im Rahmen der Probenvorbereitung für die Elektronenmikroskopie kamen zwei verschiedene Fixierungsmethoden zum Einsatz: die konventionelle chemische Fixierung, Entwässerung und Flacheinbettung von Kulturzellen und die Hochdruckgefrierung mit anschließender Gefriersubstitution. In Bezug auf die Qualität des Strukturerhalts, die beim Hochdruckgefrieren erreicht wird, wird dieser Art der Fixierung eine Überlegenheit gegenüber allen anderen Verfahren zugeschrieben. Diese allgemeine Aussage kann nicht vollständig auf die Untersuchungen an den Myoblasten übertragen werden. Für die Untersuchung der Kernmembranen sind beide Methoden geeignet, wobei der Abstand zwischen innerer und äußerer Kernmembran nach der HPF-Fixierung schärfer abgebildet wurde. Bei der Darstellung der Mitochondrien zeigten die elektronenmikroskopischen Aufnahmen nach dem Hochdruckgefrieren bessere und schärfere Ergebnisse. Die Kernporen waren bei beiden Fixierungsmethoden gut erkennbar. Beim Vergleich der gesunden und erkrankten Myoblasten wiesen die Kontrollzellen deutlich weniger Auffälligkeiten auf als die Myoblasten von FSHD-Patienten. Innere und äußere Kernmembran verliefen bei den Kontrollzellen meist parallel und die Mitochondrien zeigten in den meisten Fällen eine typische wurmartige, längliche Form mit Cristae. Dies traf sowohl für die konventionelle Fixierung als auch für das Hochdruckgefrieren zu. Die erkrankten Myoblasten wiesen im Vergleich zur Kontrolle bei beiden Fixierungsmethoden deutliche Auffälligkeiten in der Mitochondrien-Morphologie auf. Neben einer oft großen Variationsbreite hinsichtlich Form und Länge war auch das teilweise Fehlen der Cristae festzustellen. Bei Betrachtung der Kernhülle fielen jedoch deutliche Unterschiede zwischen konventioneller und HPF-Fixierung auf. Die äußere Kernmembran der konventionell fixierten FSHD-Myoblasten verlief unregelmäßig und gewellt. Im Gegensatz dazu wies die Kernhülle der HPF-fixierten erkrankten Myoblasten einen erstaunlich parallelen Verlauf auf. Da bei EDMD in vorangegangenen Untersuchungen auch fluoreszenzmikroskopisch Veränderungen der erkrankten Zellen auffällig waren, wurde neben den Methoden der Elektronenmikroskopie das Vorliegen und die Verteilung verschiedener Proteine in FSHD-Myoblasten mittels indirekter Immunfluoreszenz untersucht und mit den Kontrollzellen verglichen. Zur Beurteilung der Kernhülle wurden Antikörper gegen Lamin A/C und Nukleoporine eingesetzt. Die Mitochondrien wurden mithilfe des Antikörpers ANT1/2, der an den Adenin-Nukleotid-Translokator der inneren Mitochondrienmembran bindet, untersucht. Im Gegensatz zu den Untersuchungen an EDMD-Myoblasten waren die Lamine A und C sowie die Kernporen sowohl bei den Myoblasten der FSHD-Patienten als auch bei den Kontrollzellen nachweisbar und gleichmäßig verteilt. Bei der indirekten Immunfluoreszenz mit ANT1/2 zeigten sich Unterschiede zwischen den untersuchten Myoblasten-Paaren. Durch die vorliegenden Ergebnisse ist darauf zu schließen, dass die Myoblasten von FSHD-Patienten Veränderungen Mitochondrien aufweisen. Die Untersuchungen der Kernhülle liefern abhängig von der Fixierungsmethode unterschiedliche Ergebnisse. / The autosomal dominant facioscapulohumeral muscular dystrophy (FSHD), with a prevalence of about 1:20,000, is the third most common form of hereditary myopathy. First complaints are usually observed in the second decade of life. Most affected are the muscles of the face, shoulders, upper arms, lower legs and girdle. FSHD is triggered by a gene defect affecting the long arm of chromosome four (4q35), resulting in the partial deletion of polymorphic portion D4Z4 encoding the protein DUX4. This leads to disorders in DUX4 expression, changes in myogenic gene expression, suppression of muscle cell differentiation and inhibition of muscle formation. FSHD and another form of muscular dystrophy, the Emery-Dreifuss muscular dystrophy (EDMD), show phenotypic similarities in the severity of the disease, despite different genetic causes. In previous studies, the nuclear envelope of EDMD myoblasts showed morphological abnormalities. Other studies revealed morphological changes in the mitochondria of FSHD patients. Therefore, electron micrographs of the nuclear envelope and mitochondria of FSHD myoblasts were performed and compared to the corresponding control. For this purpose, three different pairs of myoblasts were used in different passages, that is, different numbers of subcultures, with increased morphological atypia being observed in the higher passages. The cell lines used differentiate by several parameters such as age and sex of the patients. There were differences between the control cells as well as between the FSHD myoblasts. Two different fixation methods were used in sample preparation for electron microscopy: conventional chemical fixation, drainage and flat embedding of cultured cells and high-pressure freezing with subsequent freeze substitution. In terms of the quality of structure preservation achieved in high pressure freezing, this type of fixation is attributed superiority over all other methods. This general statement cannot be completely applied to the investigations on the myoblasts. For the investigation of the nuclear membranes both methods are suitable, whereby the distance between inner and outer nuclear membrane after the HPF fixation was more sharply mapped. In the representation of mitochondria, the electron micrographs after high pressure freezing showed better and sharper results. The nuclear pores were easily recognizable in both fixation methods. When comparing the healthy and diseased myoblasts, the control cells showed significantly less abnormalities than the myoblasts of FSHD patients. The inner and outer nuclear membrane were mostly parallel in the control cells, and the mitochondria in most cases showed a typical worm-like elongated form with cristae. This was true for both conventional fixation and high pressure freezing. FSHD myoblasts exhibited marked abnormalities in mitochondrial morphology compared to controls in both fixation methods. In addition to an often wide range of variation in shape and length there was also noted the partial absence of cristae. When looking at the nuclear envelope, however, there were clear differences between conventional and HPF fixation. The outer nuclear membrane of the conventionally fixed FSHD myoblasts was irregular and wavy. In contrast, the nuclear envelope of HPF fixed diseased myoblasts showed an astonishingly parallel course. Since in EDMD changes in the diseased cells were also noticeable by fluorescence microscopy, in addition to the methods of electron microscopy, the presence and distribution of various proteins in FSHD myoblasts was examined by indirect immunofluorescence and compared with the control cells. To assess the nuclear envelope, antibodies against lamin A/C and nucleoporins were used. The mitochondria were examined using the antibody ANT1 / 2, which binds to the adenine nucleotide translocator of the inner mitochondrial membrane. In contrast to the studies on EDMD myoblasts, the lamins A and C as well as the nuclear pores were detectable and evenly distributed both in the myoblasts of the FSHD patients and in the control cells. Indirect immunofluorescence with ANT1 / 2 showed differences between the investigated myoblasts. The present results suggest that the myoblasts of FSHD patients have changes in mitochondria. The investigations of the nuclear envelope provide different results depending on the fixation method.

myotubesProper muscle function depends upon the fine tuning of the different molecular components of the neuromuscular junction (NMJ). Synaptic acetylcholinesterase (AChE) is responsible for rapidly terminating neurotransmission. Neuroscientists in the field have elucidated many aspects of synaptic AChE structure, function, and localization during the last 75 years. Nevertheless, how the enzyme is regulated and targeted to the NMJ is not completely understood. In skeletal muscle the synaptic AChE form derives from two separate genes encoding the catalytic and the collagenic tail (ColQ) subunits respectively. ColQ-AChE expression is regulated by muscle activity; however, how this regulation takes place remains poorly understood. We found that over or down-regulation of ColQ is sufficient to change the levels of AChE activity by promoting assembly of higher order oligomeric forms including the collagen-tailed forms. Furthermore, when peptides containing the Proline Rich Attachment Domain (PRAD), the region of ColQ that interacts with the AChE, are fed to muscle cells or cell lines expressing AChE, they are taken up by the cells and retrogradely transported to the endoplasmic reticulum (ER)/Golgi network where they induce assembly of newly synthesize AChE into tetramers. This results in an increase, as a consequence, in total cell associated AChE activity and active tetramer secretion, making synthetic PRAD peptides potential candidates for the treatment of organophosphate pesticides and nerve gas poisoning. To study the developmental regulation of ColQ-AChE we determined the levels of ColQ and ColQ mRNA in primary quail muscle cells in culture and as a function of muscle activity. Surprisingly, we found dissociation between transcription and translation of ColQ from its assembly into ColQ-AChE indicating the importance of posttranslational controls in the regulation of AChE folding and assembly. Furthermore, we found that the vast majority of the ColQ molecules in QMCs are not assembled into ColQ-AChE, suggesting that they can have alternative function(s). Finally, we found that the levels of ER molecular chaperones calnexin, calreticulin, and particularly protein disulfide isomerase are regulated by muscle activity and they correlate with the levels of ColQ-AChE. More importantly, our results suggest that newly synthesized proteins compete for chaperone assistance during the folding process.

Šio darbo tikslas buvo nustatyti ar NAD(P)H fluorescencija, registruojama neinvaziniu fluorescenciniu metodu, gali būti naudojama kaip miogeninių ląstelių diferenciacijos žymuo, ištiriant fluorescencijos pokyčius miogeninių ląstelių diferenciacijos metu bei išaiškinant pagrindines šių pokyčių priežastis. Tyrimai parodė, kad 95 % mioblastų fluorescencijos, išmatuotos prie 460 nm emisijos, priklauso nuo NAD(P)H kiekio. Ląstelėms diferencijuojantis fluorescencija ženkliai didėja, tačiau susiejus fluorescenciją su didėjančiu baltymų kiekiu, ženklus fluorescencijos padidėjimas nustatytas tik po 10 diferenciacijos dienų. Panaudojus ląstelių metabolizmą ir NAD(P)H kiekį veikiančius veiksnius (skyriklį CCCP ir slopiklį KCN) buvo įvertinti santykiniai NADH ir NAD+ kiekiai bei NAD+/NADH santykis, kuris diferenciacijos metu mažėjo. 535 nm fluorescencijos pokyčiai diferenciacijos metu atskleidžia didėjantį FAD kiekį. Tiek NAD+/NADH santykis tiek 535 ir 460 nm fluorescencijos emisijų santykis yra patikimesni diferenciacijos rodikliai nei pati NAD(P)H fluorescencija. Šio darbo rezultatai patvirtina, kad tokie greiti, tikslūs ir neinvaziniai fluorescencijos matavimai gali būti naudingi nustatant mioblastų diferencacijos pradžią ir vyksmą bei taikytini įvairiems bandymams siekiant nustatyti vaistų ir kitų faktorių įtaką ląstelių metabolizmui. / The aim of this study is to check hypothesis that increase of fluorescence at 460 nm emission upon myoblast differentiation display alteration of NADH quantity that change NAD+/NADH ratio and could be a myoblast marker of entering into differentiation process. To evaluate NAD(P)H influence on total cell fluorescence emission intensity at 460 nm wavelenght were used metabolism effectors: carbonyl cyanide 3-chlorophenylhydrazone (CCCP) to obtain minimal NADH fluorescence; and KCN to obtain maximal NADH fluorescence. Assuming, that CCCP caused maximal oxidation and that KCN caused maximum reduction, estimated that NAD+/NADH ratio decreased upon myoblast differentiation. CCCP effect showed that about 95 % of myoblast fluorescence at 460 nm emission is dependent on NAD(P)H. The fluorescence intensity at 460 nm was increasing with myoblast differentiation. Using fluorescence measuring estimated average NADH concentration significantly increased on 10 day of differentiation compared with control cells. Changes of fluorescence intensity at 535 nm reveal accumulation of FAD upon myoblast differentiation. Therefore, the best indicator of myoblast differentiation stage is ratio of fluorescence emission at 535 and 460 nm. Our results indicate that quick, quantitative and real-time fluorescence method may be useful for non-invasive detection and evaluation of myoblast differentiation stage.

RNA Binding Motif (RBM) domain proteins RBM5 and RBM10 have been shown to influence apoptosis, cell cycle arrest and splicing in transformed cells. In this study, RBM5 and RBM10 were examined in non-transformed cells in order to gain a wider range of knowledge regarding their function. Expression of Rbm5 and Rbm10, as well as select splice variants, was examined at the mRNA and protein level throughout H9c2 skeletal and cardiac myoblast differentiation. Results suggest that Rbm5 and Rbm10 may (a) be involved in regulating cell cycle arrest and apoptosis during skeletal myoblast differentiation and (b) undergo post-transcriptional or translational regulation throughout myoblast differentiation. All in all, the expression profiles obtained in the course of this study will help to suggest a role for Rbm5 and Rbm10 in differentiation, as well as possible differentiation-specific target genes with which they may interact.

Living organisms are made up of a multitude of individual cells that are surrounded by biomolecules and fluids. It is well known that cells are highly regulated by biochemical signals; however it is now becoming clear that cells are also influenced by the mechanical forces and mechanical properties of the local microenvironment. Extracellular forces causing cellular deformation can originate from many sources, such as fluid shear stresses arising from interstitial or blood flow, mechanical stretching during breathing or compression during muscle contraction. Cells are able to sense variations in the mechanical properties (elasticity) of their microenvironment by actively probing their surroundings by utilizing specialized proteins that are involved in sensing and transmitting mechanical information. The actin cytoskeleton and myosin-II motor proteins form a contractile (actomyosin) network inside the cell that is connected to the extracellular microenvironment through focal adhesion and integrin sites. The transmission of internal actomyosin strain to the microenvironment via focal adhesion sites generates mechanical traction forces. Importantly, cells generate traction forces in response to extracellular forces and also to actively probe the elasticity of the microenvironment. Many studies have demonstrated that extracellular forces can lead to rapid cytoskeletal remodeling, focal adhesion regulation, and intracellular signalling which can alter traction force dynamics. As well, cell migration, proliferation and stem cell fate are regulated by the ability of cells to sense the elasticity of their microenvironment through the generation of traction forces. In vitro studies have largely explored the influence of substrate elasticity and extracellular forces in isolation, however, in vivo cells are exposed to both mechanical cues simultaneously and their combined effect remains largely unexplored. Therefore, a series of experiments were performed in which cells were subjected to controlled extracellular forces as on substrates of increasing elasticity. The cellular response was quantified by measuring the resulting traction force magnitude dynamics. Two cell types were shown to increase their traction forces in response to extracellular forces only on substrates of specific elasticities. Therefore, cellular traction forces are regulated by an ability to sense and integrate at least two pieces of mechanical information - elasticity and deformation. Finally, this ability is shown to be dependent on the microtubule network and regulators of myosin-II activity.

Living organisms are made up of a multitude of individual cells that are surrounded by biomolecules and fluids. It is well known that cells are highly regulated by biochemical signals; however it is now becoming clear that cells are also influenced by the mechanical forces and mechanical properties of the local microenvironment. Extracellular forces causing cellular deformation can originate from many sources, such as fluid shear stresses arising from interstitial or blood flow, mechanical stretching during breathing or compression during muscle contraction. Cells are able to sense variations in the mechanical properties (elasticity) of their microenvironment by actively probing their surroundings by utilizing specialized proteins that are involved in sensing and transmitting mechanical information. The actin cytoskeleton and myosin-II motor proteins form a contractile (actomyosin) network inside the cell that is connected to the extracellular microenvironment through focal adhesion and integrin sites. The transmission of internal actomyosin strain to the microenvironment via focal adhesion sites generates mechanical traction forces. Importantly, cells generate traction forces in response to extracellular forces and also to actively probe the elasticity of the microenvironment. Many studies have demonstrated that extracellular forces can lead to rapid cytoskeletal remodeling, focal adhesion regulation, and intracellular signalling which can alter traction force dynamics. As well, cell migration, proliferation and stem cell fate are regulated by the ability of cells to sense the elasticity of their microenvironment through the generation of traction forces. In vitro studies have largely explored the influence of substrate elasticity and extracellular forces in isolation, however, in vivo cells are exposed to both mechanical cues simultaneously and their combined effect remains largely unexplored. Therefore, a series of experiments were performed in which cells were subjected to controlled extracellular forces as on substrates of increasing elasticity. The cellular response was quantified by measuring the resulting traction force magnitude dynamics. Two cell types were shown to increase their traction forces in response to extracellular forces only on substrates of specific elasticities. Therefore, cellular traction forces are regulated by an ability to sense and integrate at least two pieces of mechanical information - elasticity and deformation. Finally, this ability is shown to be dependent on the microtubule network and regulators of myosin-II activity.

Adult skeletal muscles have remarkable regenerative capacity. Muscle regeneration occurs when muscle tissue experiences injury, causing a population of normally quiescent muscle-resident stem cells, called satellite cells, to become activated. The CCAAT/enhancer binding proteins known as C/EBPs are transcription factors belonging to the bZIP family. Previous work from our lab has identified C/EBPβ as an important negative regulator of myogenesis. C/EBPβ expression is localized to muscle satellite cells and is downregulated upon induction to differentiate, mirroring the loss of Pax7 expression in early myogenesis. C/EBPβ expression also negatively regulates MyoD protein expression. Leaky ribosomal scanning of the Cebpb mRNA produces three C/EBPβ isoforms: LAP*, LAP and LIP, though the individual role of each of these isoforms has not been investigated in myoblasts. This thesis focuses on determining the role of each of the C/EBPβ isoforms during skeletal muscle differentiation. Forced expression of the C/EBPβ-LIP isoform in myoblasts led to a decrease in Myf5, MyoD, and myogenin expression under differentiation conditions when compared to empty vector controls. Further, the fusion of cells was greatly reduced following differentiation. C/EBPβ-LIP expressing cells also demonstrated a growth defect, with pronounced G1 arrest and features of senescence. In contrast, myoblasts expressing the C/EBPβ-LAP isoform has impaired differentiation, though this was not as pronounced as in C/EBPβ-LIP expressing cells and proliferated normally. While LIP is not normally expressed in primary myoblasts from healthy muscle, the ratio of LIP:LAP was increased in primary myoblasts isolated from mdx mice, an animal model for Duchenne muscular dystrophy. These findings suggest that the regulation of C/EBPβ isoform expression could regulate stem cell stamina and may contribute to defects in muscle regeneration in disease.

The aim of this project was to create a novel biodegradable, synthetic scaffold that will provide the correct topographical cues for myoblast alignment and efficient differentiation into myotubes. Skeletal muscle repair after major surgery or serious burns is often overlooked leading to poor healing and consequent loss of power in movements of affected limbs. In order to overcome this problem a tissue engineered construct could be utilised as a grafting patch to encourage further regeneration and enhance possible power to the limb. Using a biodegradable polymer can provide structural support until the tissue is established, and will be excreted by the body's natural processes as it degrades. A synthetic polymer is desirable as it can reduce the risk of immunogenic responses thus reduce risk of graft rejection. For successful in vitro growth of skeletal muscle, the cells must be encouraged to arrange themselves into parallel arrays in order for efficient fusion and consequent contraction. By incorporating the correct topographical cues into the scaffold to promote contact guidance for cellular alignment this can be achieved. Electrospinning is a reliable technique which yields highly reproducible aligned fibres from the micro- to the nanoscale. This project focuses upon creating and characterising the electrospun scaffold, checking biocompatibility with myoblasts by monitoring the topography, residual solvent within the scaffold, the mechanical properties of the scaffold, and a brief investigation into the degradation profile of the electrospun fibres. The immunogenicity of the scaffold was investigated by monitoring cytokine release from macrophages. Myoblast morphology was monitored, as was the efficiency of the cells to differentiate and their potential to become contractile myofibres. Cellular adhesion to the scaffold was also looked into by measuring the expression of integrins during early and late adhesion and on substrates with different topographies. It was found that the electrospun scaffold did not contain a significant amount of residual solvent, and macrophages were not activated any more than on tissue culture plastic. Myoblasts responded to the topography of the aligned fibres by aligning along the length of the fibres, showing elongation and bi-axial cytoskeletal arrangement after just 30 minutes culture on the aligned fibres. This elongation prompted fusion and differentiation of the myoblasts to occur faster than cells which were not exposed to the aligned topography, and this global alignment was maintained in long term culture.

La remarquable capacité de croissance musculaire des poissons est liée notamment à leur capacité à produire durablement de nouvelles fibres (hyperplasie). Nous avons cherché à caractériser au niveau cellulaire et moléculaire les propriétés intrinsèques des précurseurs myogéniques de muscle hyperplasique de la truite. Ainsi, nous avons comparé la prolifération in situ, le comportement in vitro, et les transcriptomes (ARN messagers et microARNs) de précurseurs myogéniques de muscle hyperplasique de truites juvéniles (JT) et de muscles non-hyperplasiques de truites juvéniles soumises à un jeûne prolongé (FJT) ou de truites adultes (AT). Nous avons observé un fort taux de prolifération des cellules satellites au sein du muscle hyperplasique comparé au muscle non-hyperplasique.L’analyse du transcriptome montre que les gènes surexprimés dans les précurseurs du muscle hyperplasique (JT) sont principalement impliqués dans l'activité mitochondriale, le cycle cellulaire et la différenciation myogénique. L’analyse du miRnome a mis en évidence des miRNA surexprimés chez les JT dont les cibles potentielles régulent la prolifération ou la différenciation. En accord avec ces résultats, les précurseurs myogéniques JT présentent in vitro des capacités de prolifération et de différenciation plus élevées que les précurseurs myogéniques FJT et AT. L’ensemble de nos résultats montrent que les précurseurs myogéniques extraits de muscle en croissance hyperplasique présentent, de par les expressions géniques dont ils sont le siège et leur comportement in vitro, de plus grandes capacités intrins / The dramatic increase in myotomal muscle mass in fish is related to their unique ability to lastingly produce new muscle fibres, a process termed hyperplasia. In this study, we aimed to characterize intrinsic properties of myogenic cells originating from hyperplasic fish muscle. For this purpose, we compared in situ proliferation, in vitro cell behavior and transcriptomes (RNAs and miRNAs) of myogenic precursors from hyperplasic muscle of juvenile trout (JT) and from non-hyperplastic muscle of fasted juvenile trout (FJT) and adult trout (AT). We showed an higher proliferation rate of trout satellite cells in vivo in hyperplastic muscle compared to non-hyperplastic muscle. Functional analysis of transcriptomics data showed, among the over-expressed genes in JT myogenic cells compared to AT and FJT, an enrichment in genes related to mitochondrial activity, cell cycle and myogenic differentiation.We found also an enrichment in genes involved in Notch signaling pathway, indicating a repression of quiescency markers in JT myogenic cells compared to AT and FJT. Moreover, the miRnome analysis also revealed overexpressed miRNAs in JT whose targets may regulate the proliferation and the differentiation of myogenic precursors. In line with our results, JT myogenic precursors displayed in vitro higher proliferation and differentiation capacities than FJT and AT myogenic precursors. On the whole, our results converge to support the view that myogenic cells extracted from hyperplastic muscle of juvenile trout are intrinsically more potent to form myofibres than myogenic cells extracte

京都大学 / 0048 / 新制・課程博士 / 博士(人間・環境学) / 甲第22671号 / 人博第957号 / 新制||人||227(附属図書館) / 2020||人博||957(吉田南総合図書館) / 京都大学大学院人間・環境学研究科相関環境学専攻 / (主査)教授 川本 卓男, 教授 宮下 英明, 教授 高田 穣 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DFAM