Scientists from San Raffaele Institute and the University of Milan have uncovered the developmental switch that turns embryonic into fetal muscle in mice.  The research, led by Graziella Messina and coordinated by Giulio Cossu, has been published in the February issue of Cell and identifies a single gene – called Nuclear Factor I X, Nfix – that acts as this switch.

In mammals, skeletal muscle develops in successive stages, involving different cell populations and expression of different genes.  Embryonic muscle expresses slow-contracting proteins and metabolic enzymes with low activity, corresponding to a muscle that contracts slowly. In the fetus, however, fast-contracting proteins and metabolic enzymes with high activity appear, corresponding to a muscle already efficient and similar to adult muscle.

Researchers have identified a single switch – the protein Nfix - that can move this muscle development programme from the embryonic to fetal stage.  In fact, mouse fetuses without this key protein are smaller with reduced muscle size and still express embryonic genes (see image pair on left), while embryos prematurely expressing Nfix acquire fetal characteristics, with increased muscle size (see image pair on right).

These findings shed new light on the evolution of skeletal muscle, and uncover an important gene at work in the process.  They may also help in the understanding of genetic muscle diseases, such as muscular dystrophy.

The study was supported by the European Community (Optistem, Angioscaf), European Research Council, Ministero della Ricerca (FIRB) e della Salute, Telethon, Fondazione Roma, Association Francoise contra les Myopathies (AFM) and Duchenne Parent Project (Italy).