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Robustness of vulva development in Caenorhabditis elegans

Final Activity Report Summary - ROBUSTNESS (Robustness of vulva development in Caenorhabditis elegans)

How developmental systems robustly generate invariant phenotypes despite variation in the environment is a fundamental question in biology. Although the environment is the principal source of perturbations affecting any biological system, experimental analyses have so far neglected its impact. In this project, we established the first detailed empirical analysis addressing this question using caenorhabditis vulva cell fate patterning as a study system.

C. elegans vulval formation served as a prominent experimental paradigm to elucidate intercellular signalling events involving three conserved signalling pathways, the Ras, Wnt and Notch pathways, which are key developmental pathways used throughout the animal kingdom. Here we showed that the interplay among these signalling pathways was highly flexible depending on the environment. The project resulted not only in the reveal of the condition-dependent nature of molecular and cellular mechanisms, but in the further reveal of how ecological forces could drive developmental system evolution. These discoveries indicated that the past decades of research in developmental biology, i.e. in studying development using a single wild genotype in a single laboratory environment, had only captured a fraction of the complexity underlying animal development.

Through the course of this project, we followed vulval cell fate specification of over 50 000 individuals in six different environmental conditions. The major findings were the following:
1. We showed that vulval development was highly robust, with more than 99.7 % of animals developing correctly a vulval organ, even in the most stressful conditions.
2. However, such robustness had limits. A small fraction of animals failed to develop a correct vulval phenotype. Certain developmental deviations revealed how environmental challenges impacted a developmental system and how the system relied on back-up mechanisms, such as cellular redundancy, to ensure correct formation of the vulva.
3. When examining multiple caenorhabditis genotypes and species, we found that the genetic background drastically modulated the response to environmental challenges, even though the vulval cell lineage and phenotype were identical in all caenorhabditis species. This result demonstrated how developmental mechanisms could diverge evolutionarily while generating the same final phenotype and indicated that developmental robustness itself was subject to evolution.
4. All major pathways, such as Egf, Ras, Mapk, Wnt and Notch, showed high environmental sensitivity. Moreover, the environment could profoundly alter the requirement for each pathway and crosstalk among them.
5. Using mutation accumulation lines we showed that the robustness of the vulval phenotype was maintained by natural selection. This experimental result provided the first experiment testing of how adaptive versus non-adaptive forces had shaped developmental system evolution.