Robustness is the ability of biological systems to produce invariant phenotypes despite perturbations. Development is especially robust to internal perturbations, like stochastic gene expression or mutations, and external perturbations, such as changes in environmental factors including temperature and nutrition. The highly invariant developmental patterning in Caenorhabditis elegans offers an ideal system to study the genetic and molecular mechanisms underlying developmental robustness. This work describes an experimental paradigm to discover the mechanistic basis and consequences of developmental robustness using the C. elegans seam cells as a model. Seam cells are lateral epidermal cells that are stem cell-like in their ability to produce differentiated cells and maintain proliferative potential. Through a forward genetic screen, I describe a novel role for the fusogen gene eff-1, which was previously known to drive cell fusion events, in the robustness of seam cell patterning. Furthermore, I show that eff-1 is not required for differentiation of seam cells, therefore I demonstrate that fusion is uncoupled from the differentiation programme. In another set of experiments, I show for the first time that the terminal number of seam cells in C. elegans is robust to standing genetic variation. A consequence of developmental robustness is the acquisition of cryptic genetic variation that does not modify the phenotype under normal conditions but manifests phenotypically upon perturbation. I demonstrate that the genetic background affects seam cell number at a higher developmental temperature of 25 C or upon mutations in the GATA transcription factor and target of the Wnt pathway, egl-18. CB4856 (Hawaii) suppressed the effect of temperature on the seam cell number compared to the lab reference N2 (United Kingdom), as well as lowered the expressivity of egl-18 mutations. Multiple regions of the genome were found to interact epistatically to modify egl-18 mutation expressivity, suggesting that a complex genetic architecture underlies seam cell development. Taken together, this work increases our knowledge on the robustness of seam cell patterning to various sources of variation.Open Acces
