Time course of ion channel development in Xenopus muscle induced in vitro by activin

During the process of mesoderm specification in Xenopus embryos, cells of the equatorial region are induced to form mesoderm in response to signals from the underlying endodermal cells. One mesodermal cell type resulting from this in vivo induction is skeletal muscle, which has a very specific and tightly regulated course of electrical and morphological development. Previously, electrical development could be analyzed only after neurulation, once myocytes could be morphologically identified. In vitro, activin triggers a cascade of events leading to the development of specific mesodermal tissues, including skeletal muscle; however, the precise role of activin in vivo is less clear. Much is now known about the mechanism and control of activin action, but very little is known about the subsequent time course of differentiation of activin-induced muscle. Such muscle is routinely identified by the presence of a small number of specific markers which, although they accurately confirm the presence of muscle, give little indication of the time course or quantitative aspects of muscle development. One of the most important functional aspects of muscle development is the acquisition of the complex electrical properties which allow it to function normally. Here we assess the ability of activin to drive in vitro the normal highly regulated sequence of electrical development in skeletal muscle. We find that in most, but not all, respects the normal time course of development of voltage-gated ion currents is well reproduced in activin-induced muscle. This characterization strengthens the case for activin as an agent capable of inducing the detailed developmental program of muscle and now allows for analysis of the regulation of electrical development prior to neurulation.