ALTERNATIVE TEMPORAL CONTROL-SYSTEMS FOR HYPODERMAL CELL-DIFFERENTIATION IN CAENORHABDITIS-ELEGANS

IN certain multicellular organisms, genetic regulatory systems that specify the timing of cell division, differentiation and morphogenesis 1-3 must accommodate environmental and physiological contingencies that perturb or arrest development. For example, Caenorhabditis elegans can either develop continuously through four larval stages (L1-14) or arrest indefinitely as a 'dauer larva' at the second larval (L2) moult, and later resume L3 and L4 development 4-7. 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, lin-14, lin-28 and lin-29, 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 10: lin-29 activates the switch and the other heterochronic genes regulate it indirectly by regulating lin-29. We have now examined how the proper timing of this event is specified in alternative developmental pathways. In continuously developing lin-4, lin-14 and lin-28 mutants the L/A switch occurs at abnormally early or late moults 3,8, 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.