LAMA2-congenital muscular dystrophy (LAMA2-CMD) is a neuromuscular disease triggered by mutations in LAMA2, codifying the ?2 chain of laminins 211/221, and leads to reduced muscle strength and failed muscle regeneration. Our previous studies using the dyW mouse model for LAMA2-CMD indicated that laminin 211 may play an important role during normal muscle development and growth by interacting with fetal muscle stem cells (MuSCs) and myoblasts. More specifically, we found that between embryonic day (E)17.5 and E18.5, the number of Pax7- and Myogenin-positive cells becomes reduced in dyW fetuses compared to controls and their muscle growth lags behind. Here we used a C2C12 myoblast cell line lacking Lama2 as an in vitro myogenesis model for LAMA2-CMD and found that myofiber formation was impaired in this cell line in 2D culture compared to the wildtype cell line. With the aim of dissecting out how Lama2 affects myoblast differentiation, we focused our analysis on the Nfix pathway, known to be responsible for the switch between embryonic and fetal myogenesis, and the Myogenin pathway, which leads to terminal myoblast differentiation. We analyzed mRNA and protein expression of Nfix and Myogenin and some of their targets using deep back muscles from E17.5 and E18.5 dyW-/- and wildtype fetuses, as well as C2C12 Lama2 knockout and wildtype cells grown in 2D and 3D. The data obtained so far suggest an increase in Nfix and a decrease in Myogenin expression, as well as a deregulation of their downstream targets, when Lama2 is absent, suggesting that laminin 211 normally plays a role in modulating myoblast differentiation. These findings contribute to increasing our understanding of the molecular and cellular mechanisms underlying the first steps of LAMA2-CMD, essential for the development of targeted therapies for this incurable disease.