Neurofibromatosis type 1-associated myopathy is caused by metabolic reprogramming of juvenile muscle progenitor cells in a mouse modelSigmar Stricker (Freie Universität Berlin)
Neurofibromatosis type 1 (NF1) is a multi-organ disease caused by mutations in Neurofibromin (NF1). NF1 patients frequently show reduced muscle mass and strength, impairing patients’ mobility and increasing the risk of fall. The role of NF1 in muscle and the cause for the NF1-associated myopathy is mostly unknown. Conditional loss of Nf1 in mouse muscle caused decreased postnatal growth, reduced muscle size, and fast fiber atrophy. Unexpectantly, this was fully dependent on Nf1 function in early postnatal myogenic progenitors, not mature muscle fibers. We reveal an unexpected role of Ras/Mapk signaling supporting postnatal MP quiescence in concert with Notch signaling, which is controlled by Nf1 safeguarding coordinated muscle growth and muscle stem cell pool establishment. Moreover, this suggests that Nf1-associated myopathy is a developmental disease suggesting an early postnatal time window for treatment.
Sigmar Stricker is Invited by Pascal Maire.