Micrornas In Development PDF Download

In the face of random perturbations in environment as well as genetic mutations, complex organisms manage to maintain remarkably robust developmental stability. Despite originating from a single cell and sharing a common genome, tissue-based organisms contain many different cellular phenotypes. The robustness of the developmental programs of these organisms depends on their underlying gene regulatory network (GRN), which is composed of a diverse set of mechanisms that help the cell achieve a desired state and stay there. One curiosity of tissue-based organisms is their near-universal dependence on non-coding RNAs, of which the largest class is the 18-22nt long microRNAs (miRNAs). These short RNAs typically, but not always, repress the translation of messenger RNAs (mRNAs) into functional proteins in a sequence-specific manner. Nonetheless, identifying the relationship between tissue-based organism development and miRNAs has been challenging. Within a single model organism, a large number of synthesis and functional pathways contribute to this overall effect. Furthermore, despite their overall dependence on miRNAs, it has been demonstrated that only a small subset of the total set of DNA-encoded miRNAs (the miRNAome) is required for proper development, and the loss of individual miRNAs often causes no change in phenotype. This dissertation aims to postulate a "fundamental law of miRNAs" in the development of these organisms. The complexities of miRNA-mediated gene regulation can often obscure their commonalities; by using a common abstraction of GRNs and gene expression, my aim is to show that miRNA-mediated regulation is innately tied to the notion of stem cells and cell differentiation. Using a multiple different models of gene expression and cell differentiation, I show how the specific type of regulation imparted by miRNAs can help create a stable, undifferentiated state and control the duration of that state. This role for miRNAs is supported independently by each model and agrees with experimentally-observed data.