The role of myosins in Xenopus retinal ganglion cell growth cone motil
ity in the optic tract was studied using two pharmacologic inhibitors
with different specificities. 2,3-Butanedione monoxime (BDM) disrupts
myosin-actin interactions of all myosins, and ML-7 specifically inhibi
ts activation of myosin II, Both inhibitors caused growth cones to ass
ume a collapsed morphology and decreased growth cone speed, Similar ef
fects were observed in vitro. Interestingly, the effects of the two in
hibitors, while similar, were clearly distinguishable, raising the pos
sibility that different myosins may have different functional roles in
growth cone motility, BDM caused growth cones to withdraw lamellipodi
a and some filopodia and eventually to freeze, whereas ML-7 caused tot
al collapse and retraction, Concentrations of BDM and ML-7 that had no
effect when applied independently stopped growth cones when applied s
imultaneously, suggesting that these inhibitors act synergistically on
myosin function, thus providing evidence of specificity, These result
s imply that normal growth cone motility in the molecularly and spatia
lly complex environment of the living brain requires myosin function.
(C) 1997 John Wiley & Sons, Inc.