Worm Breeder's Gazette 10(3): 124
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The heterochronic genes lin-4, lin-28 and lin-29 control the timing of specific postembryonic developmental events. We have examined how these four genes interact to control the normal timing of the four events listed below. The phenotypes of singly- mutant and multiply-mutant strains have suggested a model wherein the timing of these four events is controlled by a branched regulatory hierarchy. Dauer larva initiation . lin-14 recessive alleles cause precocious dauer larvae formation, while lin-14 semidominant alleles and lin-4 ( e912) cause retarded dauer larva formation, or, in some cases, prevent dauer larva formation altogether. lin-28 and lin-29 do not participate in the temporal control of dauer larva initiation. (See Liu and Ambros, this WBG for more details) Dauer larva differentiation. lin-14 or lin-28 mutations cause partial dauer larva differentiation, apparently as a result of temporal transformations in the fates of hypodermal cells such that some cells are either too retarded or too precocious in their temporal identity to differentiate properly even though the animal as a whole has elected to initiate dauer larva development. The partial differentiation defects of lin-14 and lin-28 recessive mutant dauer larvae are suppressed by lin-29 mutations, suggesting that these lin- 14 and lin-28 mutations affect dauer larva differentiation via lin-29. ( See also Liu and Ambros, this WBG.) VPC division. The first division of the vulva precursor cells (VPCs) occurs precociously (in the L2 stage instead of the L3 stage) in lin- 14 and lin-28 recessive mutants. Conversely, in lin-4 (e912) or lin- 14 semidominant mutants, the VPCs are variably affected in a manner that could be interpreted as a delay and/or reiteration of the first division (Chalfie, et al, Cell, 24; Ambros and Horvitz, Science, 226). lin-29 mutations do not block the lin-14 and lin-28 VPC defects. L/A switch. In the wild type, hypodermal cells switch from expressing 'larval molts' to expressing an 'adult molt' at the L4 stage. This switch involves changes in cuticle gene expression and cessation of seam cell division. Single mutations in any of these four genes cause either precocious or retarded L/A switching. A strain that lacks all four genes does not switch. A strain with a wild type lin-29 gene but which lacks the other three of these genes switches precociously, at the L2 molt. Thus, lin-29 is necessary and sufficient for L/A switching, and the other three genes likely regulate lin-29 to ensure the proper temporal specificity of the switch. The stage-specific execution of these four events (as well as certain other events not discussed here) is proposed to be governed by the branched regulatory hierarchy diagrammed below . lin-14 activity at early stages prevents early expression of these events, and then a decrease in lin-14, under the negative regulation of lin-4, allows the expression of each event at its specified time. The temporal coordination of diverse events such as these may be rooted in the fact that they share 'master regulators' such as lin-14 and lin-4. We have initiated genetic strategies to identify more specialized regulators of each event. It should be noted that Gary Ruvkun's lab has isolated mutants that form dauer larvae precociously; these could identify new lin-14 alleles or new gene(s), for example, regulators of dauer initiation. [See Figure 1]