Cultured myf5 null and myoD null muscle precursor cells display distinct growth defects

Myf-5 and MyoD are the two muscle regulatory factors expressed from the myo blast stage to maintain the identity and to promote the subsequent differen tiation of muscle precursor cells. To get insight into their role we have s tudied the capacity to proliferate and to differentiate of myf-5 and myoD n ull myoblasts in primary cultures and in the subsequent passages. Our resul ts indicate that myf-5 null myoblasts differ from wild type (wt) myoblasts in that they undergo precocious differentiation: they become myogenin- and troponin T-positive and fail to incorporate bromodeoxyuridine (BrdU) under culture conditions and at a time when wt cells are not yet differentiated a nd continue to proliferate. In primary cultures of myoD null cells, up to 6 0% of the cells were scored as myoblasts on the basis of the expression of myf-5. These myoD-deficient myoblasts, unlike myoD-expressing cells, were p oorly differentiating and displayed a severe growth defect that led to thei r elimination from the cultures: within a few passages myoblasts were absen t from myoD-deficient cultures, which mostly consisted of senescent cells. That a null mutation in either gene reduces the proliferative potential of cultured myoblasts raises the possibility that Myf-5 and MyoD serve prolife ration of muscle precursor cells. (C) 2000 Editions scientifiques et medica les Elsevier SAS.