CREB mediates the C. elegans dauer polyphenism through direct and cell-autonomous regulation of TGF-β expression

Animals can adapt to dynamic environmental conditions by modulating their developmental programs. Understanding the genetic architecture and molecular mechanisms underlying developmental plasticity in response to changing environments is an important and emerging area of research. Here, we show a novel role of cAMP response element binding protein (CREB)-encoding crh-1 gene in developmental polyphenism of C. elegans. Under conditions that promote normal development in wild-type animals, crh-1 mutants inappropriately form transient pre-dauer (L2d) larva and express the L2d marker gene. L2d formation in crh-1 mutants is specifically induced by the ascaroside pheromone ascr#5 (asc-omega C3; C3), and crh-1 functions autonomously in the ascr#5-sensing ASI neurons to inhibit L2d formation. Moreover, we find that CRH-1 directly binds upstream of the daf-7 TGF-beta locus and promotes its expression in the ASI neurons. Taken together, these results provide new insight into how animals alter their developmental programs in response to environmental changes. Author summary C. elegans exhibits polyphenic development that is regulated by environmental conditions. Newly hatched larvae of C. elegans sense and integrate food availability and population density to determine whether to undergo normal reproductive development or arrest as non-aging, stress-resistant dauer. Dauer entry in C. elegans is proceeded by a commitment to either L2d, an obligate dauer precursor, or reproductive growth. Here, we find a flp-8 neuropeptide gene as the bona fide L2d marker and show that the crh-1 gene controls the L2d formation by direct regulation of daf-7 TGF-beta expression. Identification of this gene, as well as the novel L2d marker, now provides a unique opportunity to study the under-explored L2d formation of C. elegans.