Dynamic remodeling of septin structures fine-tunes myogenic differentiation
Vladimir Ugorets,
Paul-Lennard Mendez,
Dmitrii Zagrebin,
Giulia Russo,
Yannic Kerkhoff,
Georgios Kotsaris,
Jerome Jatzlau,
Sigmar Stricker,
Petra Knaus
Affiliations
Vladimir Ugorets
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Signal Transduction Group, 14195 Berlin, Germany
Paul-Lennard Mendez
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Signal Transduction Group, 14195 Berlin, Germany; Max Planck Institute for Molecular Genetics, IMPRS-Biology and Computation, 14195 Berlin, Germany
Dmitrii Zagrebin
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Signal Transduction Group, 14195 Berlin, Germany
Giulia Russo
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany
Yannic Kerkhoff
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Bionanointerfaces Group, 14195 Berlin, Germany
Georgios Kotsaris
Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Freie Universität Berlin, Institute of Chemistry and Biochemistry, Musculoskeletal Development and Regeneration Group, 14195 Berlin, Germany
Jerome Jatzlau
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Signal Transduction Group, 14195 Berlin, Germany
Sigmar Stricker
Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Freie Universität Berlin, Institute of Chemistry and Biochemistry, Musculoskeletal Development and Regeneration Group, 14195 Berlin, Germany
Petra Knaus
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Signal Transduction Group, 14195 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Corresponding author
Summary: Controlled myogenic differentiation is integral to the development, maintenance and repair of skeletal muscle, necessitating precise regulation of myogenic progenitors and resident stem cells. The transformation of proliferative muscle progenitors into multinuclear syncytia involves intricate cellular processes driven by cytoskeletal reorganization. While actin and microtubles have been extensively studied, we illuminate the role of septins, an essential yet still often overlooked cytoskeletal component, in myoblast architecture. Notably, Septin9 emerges as a critical regulator of myoblast differentiation during the initial commitment phase. Knock-down of Septin9 in C2C12 cells and primary mouse myoblasts accelerates the transition from proliferation to committed progenitor transcriptional programs. Furthermore, we unveil significant reorganization and downregulation of Septin9 during myogenic differentiation. Collectively, we propose that filmamentous septin structures and their orchestrated reorganization in myoblasts are part of a temporal regulatory mechanism governing the differentiation of myogenic progenitors. This study sheds light on the dynamic interplay between cytoskeletal components underlying controlled myogenic differentiation.
