In certain multicellular organisms, genetic regulatory systems that specify the timing of cell division, differentiation and morphogenesis must accommodate environmental and physiological contingencies that perturb or arrest development. For example, Caenorhabditis elegans can either develop continuously through four larval stages (L1-L4) or arrest indefinitely as a 'dauer larva' at the second larval (L2) moult, and later resume L3 an dL4 development. At the larva-to-adult (L4) moult of both continuous and 'post-dauer' development, hypodermal cells switch (the 'L/A switch') from a proliferating state to the terminally differentiated state. Four temporal regulators, lin-4
, have been identified in C. elegans by mutations that cause precocious or retarded expression of stage-specific post-embryonic development events, including the L/A switch (refs 3, 8, 9; Fig. 1a). These genes have been organized into a genetic pathway that controls the timing of the L/A switch during continuous development; lin-29
activates the switch and the other heterochronic genes regulate it indirectly by regulating lin-29
. We have now examined how proper timing of this event is specified in alternative developmental pathways. In continuously developing lin-4
mutants the L/A switch occurs at abnormally early or late moults, but during post-dauer development of the same mutants the L/A switch occurs normally. Thus hypodermal cell differentiation is regulated by separate temporal control systems, depending on the developmental history.