Physiological Starvation PromotesCaenorhabditis elegansVulval Induction

Abstract

Studying how molecular pathways respond to ecologically relevant environmental variation is fundamental to understand organismal development and its evolution. Here we characterize how starvation modulates Caenorhabditis elegans vulval cell fate patterning – an environmentally sensitive process, with a nevertheless robust output. Past research has shown many vulval mutants affecting EGF-Ras-MAPK, Delta-Notch and Wnt pathways to be suppressed by environmental factors, such as starvation. Here we aimed to resolve previous, seemingly contradictory, observations on how starvation modulates levels of vulval induction. Using the strong starvation suppression of the Vulvaless phenotype of lin-3/egf reduction-of-function mutations as an experimental paradigm, we first tested for a possible involvement of the sensory system in relaying starvation signals to affect vulval induction: mutation of various sensory inputs, DAF-2/Insulin or DAF-7/TGF-β signaling did not abolish lin-3(rf) starvation suppression. In contrast, nutrient deprivation induced by mutation of the intestinal peptide transporter gene pept-1 or the TOR pathway component rsks-1 (the ortholog of mammalian P70S6K) very strongly suppressed lin-3(rf) mutant phenotypes. Therefore, physiologically starved animals induced by these mutations tightly recapitulated the effects of external starvation on vulval induction. While both starvation and pept-1 RNAi were sufficient to increase Ras and Notch pathway activities in vulval cells, the highly penetrant Vulvaless phenotype of a tissue-specific null allele of lin-3 was not suppressed by either condition. This and additional results indicate that partial lin-3 expression is required for starvation to affect vulval induction. These results suggest a cross-talk between nutrient deprivation, TOR-S6K and EGF-Ras-MAPK signaling during C. elegans vulval induction.

Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

“…Similar redundant relationships between redundant partners exist in many other contexts in the animal. Notably, the relative importance of Ras, Notch, and Wnt signals in vulva induction differ in various genetic backgrounds (Milloz et al, 2008; Gleason et al, 2002) and physiological conditions (Braendle and Félix, 2008; Grimbert et al, 2018), resulting in flexibility in the system. While vulval development in C. elegans, when grown under standard laboratory conditions, predominantly favors utilization of the EGF/Ras signaling pathway (Braendle and Félix, 2008), Wnt is the predominant signaling pathway in the related Pristionchus pacificus , which is ~250 MY divergent (Zheng et al, 2005; Tian et al, 2008).…”

TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging

“…In certain vulvaless mutants with reduced signaling, starvation has been shown to restore vulval fates (Euling and Ambros 1996). A recent study demonstrated that loss of pept-1 was equivalent to starvation in suppressing the vulvaless phenotype caused by a partial loss-of-function allele in the lin-3/ EGF gene (Grimbert et al 2018) (see Upstream inputs to TOR signaling for discussion on pept-1). Moreover, let-363(RNAi) or rsks-1(2) also displayed significant suppression, albeit not as strong as that by pept-1(-).…”

Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

“…Many other similar redundant relationships between redundant partners exist in the animal. Notably, the relative importance of Ras, Notch, and Wnt signals in vulva induction differ in various genetic backgrounds [6,65] and physiological conditions [111,112], resulting in flexibility in the system. While vulval development in C. elegans, when grown under standard laboratory conditions, predominantly favors utilization of the EGF/Ras signaling pathway [111], Wnt is the predominant signaling pathway in the related Pristionchus pacificus , which is ∼250 MY divergent [113].…”