Academic journal article Genetics

The Developmental Timing Regulator Hbl-1 Modulates the Dauer Formation Decision in Caenorhabditis Elegans

Academic journal article Genetics

The Developmental Timing Regulator Hbl-1 Modulates the Dauer Formation Decision in Caenorhabditis Elegans

Article excerpt

ABSTRACT

Animals developing in the wild encounter a range of environmental conditions, and so developmental mechanisms have evolved that can accommodate different environmental contingencies. Harsh environmental conditions cause Caenorhabditis elegans larvae to arrest as stress-resistant "dauer" larvae after the second larval stage (L2), thereby indefinitely postponing L3 cell fates. HBL-1 is a key transcriptional regulator of L2 vs. L3 cell fate. Through the analysis of genetic interactions between mutations of hbl-1 and of genes encoding regulators of dauer larva formation, we find that hbl-1 can also modulate the dauer formation decision in a complex manner. We propose that dynamic interactions between genes that regulate stage-specific cell fate decisions and those that regulate dauer formation promote the robustness of developmental outcomes to changing environmental conditions.

ACHIEVING the correct outcome of developmental processes is essential for survival and fitness in animal species. Therefore, developmental outcomes must be robust to the range of environmental conditions experienced by animals developing in the wild. While muchisunderstood about genetic pathways that regulate temporal and spatial cell fate specification, less is known about how these pathways are integrated with pathways that regulate the response to environmental cues. A dramatic example of a response to environmental cues is dauer diapause in Caenorhabditis elegans. In favorable environmental conditions,C. elegans larvae progress rapidly and continuously through four larval stages prior to adulthood (Sulston and Horvitz 1977). However, unfavorable environmental cues sensed in the first larval stage (L1) cause larvae to enter the predauer L2d stage, which is .50% longer than the rapid L2 stage (Golden and Riddle 1984). During the extended L2d stage, L3 cell fates are temporarily postponed while larvae continue to sense their environment and prepare for the possibility of continued harsh conditions. At the end of L2d, larvaemake a choice between one of two distinct life histories: (1) to continue with developmental progression, molt to the L3 stage, and express L3 cell fates or (2) to interrupt development by entry to the stress-resistant dauer diapause, thereby indefinitely postponing L3 cell fates (Cassada and Russell 1975; Golden and Riddle 1984). Thus, the timing of expression of L3 cell fates is inextricably linked to theanimal's decision of whether or not to enter the dauer diapause. This suggests that pathways regulating stage-specific cell fate decisions are coordinated with pathways that regulate dauer diapause.

The dauer formation decision occurs in response to environmental cues, including temperature, food supply, and population density. These cues are perceived by sensory neurons, resulting in up- or downregulation of two partially parallel signaling pathways, TGFb and insulin-/insulin-growth-factor-1-like (IIS). These two pathways in turn regulate the activity of the third major dauer formation pathway, nuclear hormone receptor signaling (for review see Fielenbach and Antebi 2008). Favorable environmental cues lead to upregulation of the TGFb encoded by daf-7 (Ren et al. 1996; Schackwitz et al. 1996). High DAF-7/TGFb signaling opposes the activity of the downstream transcription factor DAF-3/ SMAD that complexes with DAF-5/Sno-Ski to regulate target gene expression (Patterson et al.1997; Da Graca et al. 2004). Also in favorable environmental conditions, the insulin-like receptor (InsR) DAF-2 is activated by one or more of -40 insulin-related proteins (Kimura et al. 1997; Pierce et al. 2001). High DAF-2/InsR activity opposes the activity of the downstream transcription factor DAF-16/FOXO (Lin et al. 1997; Ogg et al. 1997). When active, both DAF-16 and DAF-3-DAF-5 promote dauer formation by affecting expression of downstream genes (Thatcher et al. 1999; Jensen et al. 2006), including daf-9 (Gerischet al. 2001;GerischandAntebi 2004; Mak and Ruvkun 2004; Motola et al. …

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