TEMPORAL RESTRICTION OF MYOD INDUCTION AND AUTOCATALYSIS DURING XENOPUS MESODERM FORMATION

In Xenopus, the activation of the myogenic determination factors MyoD and Myf-5 in the muscle-forming region of the embryo occurs in respons e to mesoderm-inducing factors (MIFs). Different members of the FGF, T GF-beta, and Wnt protein families have been implicated in this process , but how MIFs induce the myogenic regulators is not known. For MyoD, the induction process map serve to locally stabilize a transient burst of ubiquitous transcription at the midblastula transition, possibly b y triggering MyoD's autocatalytic loop. Here we have sought to disting uish separate activating functions during MyoD induction by analyzing when MyoD responds to different MIF signaling or to MyoD autoactivatio n. We show that MyoD induction depends on the developmental age of the induced cells, rather than on the type or time point of inducer appli cation. At the permissive time, de novo MyoD induction by Activin requ ires less than 90 min, arguing for an immediate response, rather than a series of inductive events. MyoD autoactivation is direct, but subje ct to the same temporal restriction as MyoD induction by MIF signaling . Further evidence implicating MyoD autocatalysis as an essential comp onent of the induction process comes from the observation that both au tocatalysis and induction of MyoD are selectively repressed by a domin ant-negative MyoD mutant. In summary, our observations let us conclude that MyoD's expression domain in the embryo results from an interplay of timed changes in cellular competence, pleiotropic signaling pathwa ys, and autocatalysis. (C) 1998 Academic Press.