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.

Four Events in the Life of a Worm

Victor Ambros and Zhongchi Liu

Figure 1

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 
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 
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 
[See Figure 1]

Figure 1