Worm Breeder's Gazette 10(3): 125
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.
Under unfavorable living conditions, C. elegans can elect to develop as a dauer larva. In the wild type, dauer larva formation occurs only at the L2 molt. We have investigated how mutations of heterochronic genes lin-4, lin-28, and lin-29 affect the stage-specificity of dauer larva formation. Our results are summarized as follows: [See Figure 1] In the table, 'D' stands for 'dauer defective'; 'P', 'precocious dauer larva' formed at L1 molt; 'R', 'retarded dauer larva' formed at L3 molt; 'N', 'normal dauer larva' formed at L2 molt; 'ND', 'not done'. '-', loss of function allele; '+', wt allele; '++', gain of function allele. The first column shows the dauer formation phenotype of single heterochronic mutants, the other columns show dauer formation in doubly-mutant strains carrying the corresponding mutations at the top and left. Our results suggest that lin-14 level may regulate the stage- specificity of dauer larva formation. In mutants, an abnormally high level of lin-14 r lin-14 (++/++) ) delays or inhibits dauer larva formation, whereas an abnormally low level of lin- 14 leads to the formation of precocious dauer larvae. A lin-4 loss of function mutation, e912, is similar to lin-14 ( ++/++) gain of function mutations in that it prevents dauer formation. This observation, together with the fact that lin-14 (-/-) is epistatic to lin-4 (-/-) for dauer formation (see above table) seems to indicate that lin-4 exerts its function indirectly by negatively regulating lin-14 activity. lin-28(-/-) mutants, which are otherwise severely precocious, do not form precocious dauer larvae nor do lin-28 mutations block precocious, retarded, or defective dauer larva formation caused by lin-14 or lin-4 mutations. Similarly, lin-29(-/-) mutants, being retarded, do not lead to retarded dauer larva formation nor do lin-29 mutations block heterochronic dauer larva formation in caused by lin-14 and lin-4 mutations. Thus, lin-4 and lin-14 regulate the stage-specificity of dauer larva formation but lin-28 and lin-29 do not (see also Ambros,and Liu this WBG). [See Figure 2] All four heterochronic genes seem to participate in the regulation of an aspect of dauer larva development distinct from the stage- specificity of dauer initiation. lin-14 and lin-28 mutations often lead to the formation of incompletely differentiated dauer larvae. Certain regions of the cuticles in these incompletely differentiated dauer larvae are not fully constricted and lack dauer lateral alae. However, these incomplete dauer larvae are often SDS-resistant and have arrested their development at normal, precocious, or retarded stages depending on their genotypes (see above table). We interpret the incomplete dauer larva phenotype of these heterochronic mutants as reflecting a variable temporal transformation in the fates of cells such that some cells may be 'too precocious' or 'too retarded' relative to other cells of the same animal. As a consequence, these affected cells fail to execute dauer larva differentiation, although the animal as a whole has elected to initiate dauer larva development. Thus, we propose that dauer larva development is temporally regulated at two levels: one is the decision by the animal to initiate dauer development at a certain stage, the other involves the acquisition of an appropriate temporal identity for dauer larva differentiation by individual hypodermal cells. lin-29(-/-) mutations, which do not cause incomplete dauer larva formation, suppress the incomplete dauer larva defect caused by lin-28(-/-) mutations and (according to preliminary results) lin-14(-/-) mutants . This observation suggests that the absence of lin-29 activity during early stages of larval development may be necessary for complete dauer larva differentiation. Our study of incomplete dauer larva formation has lead to a hierarchical pathway for dauer larva differentiation, wherein lin-4 negatively regulates lin-14; ly regulates lin- 28; ly regulates lin-29; and lin-29 negatively regulates dauer larva differentiation (see also Ambros and Liu, this WBG). [See Figure 3]
