Dictyostelium erasure mutant HI4 abnormally retains development-specific mRNAs during dedifferentiation

Abstract

The Dictyostelium mutant HI4 progresses through morphogenesis normally, but is defective in the reverse program of dedifferentiation. In contrast to dedifferentiating wild-type cells, HI4 cells retain the capacity to rapidly reaggregate well after the “erasure event” employing a nonchemotactic aggregation mechanism involving random collisions and cohesion. They also do not lose contact sites A (gp80) at the prescribed time in the dedifferentiation program. HI4 cells accumulate transcripts of the cysteine protease gene CP2 (formerly referred to as 16G1) and the cohesion glycoprotein gene gp80 at the correct times in the morphogenetic program, but abnormally retain these transcripts at high levels well after the prescribed times at which they are lost in wild-type cells during the reverse program of dedifferentiation. The retention of these mRNAs in HI4 cells after the erasure event is not due to abnormal maintenance of a high level of intracellular cAMP during dedifferentiation. The rapid reduction in the level of gp80 transcript which can be effected by the addition of cAMP prior to the erasure event in wild-type cells is also retained by HI4 cells well after the erasure event. The results suggest that cells possess at least two mechanisms for the reduction of gp80 transcript. One involves the immediate response to cAMP and may function during the forward program of development. The second functions specifically during the reverse program of dedifferentiation. It is this latter, erasure-specific mechanism which is selectively defective in the HI4 variant.