Mc. Delfini et al., Delta 1-activated Notch inhibits muscle differentiation without affecting Myf5 and Pax3 expression in chick limb myogenesis, DEVELOPMENT, 127(23), 2000, pp. 5213-5224
The myogenic basic helix-loop-helix (bHLH) transcription factors, Myf5, Myo
D, myogenin and MRF4, are unique in their ability to direct a program of sp
ecific gene transcription leading to skeletal muscle phenotype, The observa
tion that Myf5 and MyoD can force myogenic conversion in non-muscle cells i
n vitro does not imply that they are equivalent. Tn this paper, we show tha
t Myf5 transcripts are detected before those of MyoD during chick limb deve
lopment. The Myf5 expression domain resembles that of Pax3 and is larger th
an that of MyoD, Moreover, Myf5 and Pax3 expression is correlated with myob
last proliferation, while MyoD is detected in post-mitotic myoblasts, These
data indicate that Myf5 and MyoD are involved in different steps during ch
ick limb bud myogenesis, Myf5 acting upstream of MyoD, The progression of m
yoblasts through the differentiation steps must be carefully controlled to
ensure myogenesis at the right place and time during wing development, Beca
use Notch signalling is known to prevent differentiation in different syste
ms and species, we sought to determine whether these molecules regulate the
steps occurring during chick limb myogenesis, Notch1 transcripts are assoc
iated with immature myoblasts, while cells expressing the ligands Delta1 an
d Serrate2 are more advanced in myogenesis, Misexpression of Delta1 using a
replication-competent retrovirus activates the Notch pathway, After activa
tion of this pathway, myoblasts still express Myf5 and Pax3 but have downre
gulated MyoD, resulting in inhibition of terminal muscle differentiation. W
e conclude that activation of Notch signalling during chick limb myogenesis
prevents Myf5-expressing myoblasts from progressing to the MyoD-expressing
stage.