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Differential regulation of myosin heavy chains defines new muscle domains in zebrafish
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
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2014 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 25, no 8, 1384-1395 p.Article in journal (Refereed) Published
Abstract [en]

Numerous muscle lineages are formed during myogenesis within both slow-and fast-specific cell groups. In this study, we show that six fast muscle-specific myosin heavy chain genes have unique expression patterns in the zebrafish embryo. The expression of tail-specific myosin heavy chain (fmyhc2.1) requires wnt signaling and is essential for fast muscle organization within the tail. Retinoic acid treatment results in reduced wnt signaling, which leads to loss of the fmyhc2.1 domain. Retinoic acid treatment also results in a shift of muscle identity within two trunk domains defined by expression of fmyhc1.2 and fmyhc1.3 in favor of the anteriormost myosin isoform, fmyhc1.2. In summary, we identify new muscle domains along the anteroposterior axis in the zebrafish that are defined by individual nonoverlapping, differentially regulated expression of myosin heavy chain isoforms.

Place, publisher, year, edition, pages
American Society for Cell Biology , 2014. Vol. 25, no 8, 1384-1395 p.
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-92681DOI: 10.1091/mbc.E13-08-0486ISI: 000339649400017PubMedID: 24523292OAI: oai:DiVA.org:umu-92681DiVA: diva2:742410
Available from: 2014-09-01 Created: 2014-09-01 Last updated: 2017-12-05Bibliographically approved
In thesis
1. The role of Six1 in muscle progenitor cells and the establishment of fast-twitch muscle fibres
Open this publication in new window or tab >>The role of Six1 in muscle progenitor cells and the establishment of fast-twitch muscle fibres
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Myogenesis is the process of skeletal muscle tissue formation where committed muscle progenitor cells differentiate into skeletal muscle fibres. Depending on the instructive cues the muscle progenitor cells receive they will differentiate into specific fibre types with different properties. The skeletal muscle fibres can be broadly classified as fast-twitch fibres or slow-twitch fibres, based on their contractile speed. However, subgroups of fast- and slow-twitch fibres with different metabolic properties, endurance and different isoforms of sarcomeric components have also been identified, adding complexity to the process of muscle tissue patterning. The skeletal muscle tissue has the capacity to regenerate throughout life. Upon muscle tissue damage muscle satellite cells are recruited to the area of injury where they proliferate and either form new fibres similar to those damaged, or fuse with existing fibres.

This thesis aims to investigate the process of muscle progenitor cell proliferation and differentiation, as well as the fast-twitch fibre formation and muscle tissue patterning in the zebrafish embryo.

I present results identifying the previously uncharacterised gene myl1, encoding an alkali-like myosin light chain, which is specifically expressed in fast-twitch muscle progenitors before fibre formation. Furthermore, I introduce data showing that the transcription factor six1 is expressed in Pax7+ muscle progenitor cells, which has been reported to contribute to part of the fast-twitch muscle tissue as well as to a pool of quiescent muscle satellite cells. With support from the presented data, I hypothesise that six1 keeps the Pax7+ muscle progenitor cells in a proliferative state and consequently prevents them from differentiating into muscle fibres. In addition, I demonstrate that the zebrafish fast-twitch muscle fibres can be divided into different subgroups that express unique forms of fast myosin heavy chain genes along the anterior-posterior (head-tail) axis, and that this subspecification depends on a balance between RA and Wnt signalling.

Collectively I propose a previously unknown role for Six1 in zebrafish Pax7+ muscle progenitor cell proliferation and differentiation. Furthermore, I present novel data suggesting that distinct regions of the zebrafish body musculature are composed of different fast-twitch fibre types, and that this regionalisation is conserved in adult zebrafish.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2014. 47 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1684
Keyword
Myogenesis, zebrafish, muscle fibre, patterning, fmyhc, myl1, Six1, Pax7
National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-95849 (URN)978-91-7601-161-4 (ISBN)
Public defence
2014-12-05, Hörsal B, Unod T9, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2014-11-14 Created: 2014-11-06 Last updated: 2014-11-14Bibliographically approved

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Nord, HannaBurguiere, Anne-CecileMuck, JoschaNord, ChristofferAhlgren, Ulfvon Hofsten, Jonas
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