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Identified the role of the transcription factor Nfix in skeletal muscle regeneration

Skeletal muscle is the tissue responsible for posture, locomotion and breathing. It is a heterogeneous tissue, composed by muscle fibers that differ in terms of dimensions, shape and contractile protein content, to fulfil the needs of vertebrate body.
This heterogeneity derives, at least in part, from the presence of different classes of myogenic progenitors: embryonic and fetal myoblasts and adult satellite cells. We previously demonstrated that Nfix is necessary for the transcriptional switch from embryonic to fetal myogenesis, a crucial checkpoint in skeletal muscle development (Messina et al., Cell 2010).
The aim of this study was to determine if Nfix could play a role also during post-natal myogenesis and regeneration, processes that are mainly driven by satellite cells, the adult muscle resident stem cells.
We observed that Nfix is expressed by satellite cells, where it plays a role in controlling the proper timing of skeletal muscle regeneration upon acute damage.
Absence of Nfix leads in fact to an altered muscle phenotype, a slower-twitching musculature and, most interestingly, a delayed regenerative capacity with respect to WT controls. We also identified the mechanism of action of Nfix, which is able to modulate expression of Myostatin, a very well characterized inhibitor of muscle growth and regeneration.
This study will have an impact on both physiology and pathophysiology of skeletal muscle. In fact, defining the molecular mechanisms regulating the correct timing of skeletal muscle regeneration is a crucial point to identify a translational approach for the treatment of Muscular Dystrophies, which are typical chronic degenerative pathologies.
The article was also selected to represent the Cover Image of Cell Reports Issue that will be published the 8 of March 2016.
This work was funded by important national and European fundings: the ERC Starting Grant 2011-RegeneratioNfix and the FIRB-Futuro in Ricerca 2010 (MIUR).


Università degli Studi di Milano

Dipartimento di Bioscienze

Prof. Graziella Messina

26 February 2016
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