O. Coutelle et al., Hedgehog signalling is required for maintenance of myf5 and myoD expression and timely terminal differentiation in zebrafish adaxial myogenesis, DEVELOP BIO, 236(1), 2001, pp. 136-150
Hedgehog proteins have been implicated in the control of myogenesis in the
medial vertebrate somite. In the mouse, normal epaxial expression of the my
ogenic transcription factor gene myf5 is dependent on Sonic hedgehog. Here
we examine in zebrafish the interaction between Hedgehog signals, the expre
ssion of myoD family genes, including the newly cloned zebrafish myf5, and
slow myogenesis. We show that Sonic hedgehog is necessary for normal expres
sion of both myf5 and myoD in adaxial slow muscle precursors, but not in la
teral paraxial mesoderm. Expression of both genes is initiated normally in
rostral presomitic mesoderm in sonic you mutants, which lack all Sonic hedg
ehog. Similar initiation continues during tailbud outgrowth when the cells
forming caudal somites are generated. However, adaxial cells in sonic you e
mbryos are delayed in terminal differentiation and caudal adaxial cells fai
l to maintain myogenic regulatory factor expression. Despite these defects,
other signals are able to maintain, or reinitiate, some slow muscle develo
pment in sonic you mutants. In the cyclops mutant, the absence of floorplat
e-derived Tiggywinkle hedgehog and Sonic hedgehog has no discernible effect
on slow adaxial myogenesis. Similarly, the absence of notochord-derived So
nic hedgehog and Echidna hedgehog in mutants lacking notochord delays, but
does not prevent, adaxial slow muscle development. In contrast, removal of
both Sonic hedgehog and a floorplate signal, probably Tiggywinkle hedgehog,
from the embryonic midline in cyclops;sonic you double mutants essentially
abolishes slow myogenesis. We conclude that several midline signals, likel
y to be various Hedgehogs, collaborate to maintain adaxial slow myogenesis
in the zebrafish embryo. Moreover, the data demonstrate that, in the absenc
e of this required Hedgehog signalling, expression of myf5 and myoD is insu
fficient to commit cells to adaxial myogenesis. (C) 2001 Academic Press.