The cell cycle, myoblast differentiation and prostaglandin as a developmental signal

Abstract

The duration of the cell cycle in primary cultures of proliferating chick myoblasts was determined. The myoblasts were found to have a mean G1 of 2.7 hr, S of 6.0 hr, G2 of 2.8 hr, and M of 0.8 hr. 10−7M Prostaglandin E1 (PGE1) produces a transient rise in the intracellular level of cyclic AMP and provokes a burst of precocious fusion 5–7 hr later in the myoblast cultures. Use was made of this finding to examine the possibility that the subpopulation of cells which responds to the rise in intracellular cyclic AMP is in a specific part of its cell cycle. [3H]Thymidine was added to the myoblast cultures at discrete intervals before exposure to the PG 34 hr after plating. Six and seven hours later (i.e., at 40–41 hr) the cultures were fixed and autoradiographed and the appearance of labeled nuclei in myotubes was assessed. Only a basal level of labeled nuclei appeared in myotubes in control cultures and in those exposed to [3H]thymidine for less than 4 hr before PGE1 addition. With increases in the time of exposure to [3H]thymidine above the minimum of 4 hr, increasing numbers of labeled nuclei appeared in myotubes. Taking into account the duration of the phases of the myoblast's cell cycle, it is concluded that the cells which respond to PGE1 by fusing 5–7 hr later are in the G1 phase of their cell cycle. From these and related results, a model of cellular decision making in myoblast differentiation is proposed.