MicroRNAs Protect the Robustness of Distal Tip Cell Migrations from Temperature Changes in Caenorhabditis elegans: A Dissertation

Abstract

microRNAs play an important role in protecting biological robustness during development. Biological robustness is the ability to maintain a consistent output despite variation in input, such as transcriptional noise or environmental stresses. Here, we show that the conserved microRNAs mir-34 and mir-83 promote the robust migration of the distal tip cells in Caenorhabditis elegans when stressed by changing environmental temperature. Our results show that distal tip cell migration is sensitive to temperature changes occurring within a two hour period during the first larval stage. mir-34 and mir-83 protect distal tip cell migration by regulating potential targets cdc-42, pat-3, and peb-1. cdc-42 and pat-3 are known components of the integrin signaling network controlling pathfinding during migration, while the involvement of peb-1 is a novel finding. Additionally, loss of the two microRNAs leads to a reduction in both fecundity and lifespan, suggesting that the loss of developmental robustness leads to a decrease in fitness. mir-34 and mir-83 are not only conserved in higher organisms, but duplicated. Both have been implicated as tumor suppressor genes in mammalian work. Our work has found a role for both microRNAs in integrin-regulated cell migrations that is potentially conserved in higher organisms. Additionally, our work supports the growing appreciation for the role of microRNAs in both stress response and promoting developmental robustness.