Transcriptional and post-transcriptional mechanisms of cell diversification

The evolution of multicellularity occurred hand in hand with the diversification of cell types with disparate morphologies and functions. This segregation of function across different cell types enabled astounding animal complexity; but at the same time, extreme specializations of individual cell types often leave them vulnerable to genetic or environmental variations. Therefore, understanding how cells diversify and what makes them unique, is important to understand animal physiology in health and disease. Our work has explored two aspects of animal cell diversification, with a focus on the gene-regulatory mechanisms that underlie this process. First, we ask how different cell types are specified along the developmental process. Specifically, we have focused on how cell identities are defined by their different transcriptional histories, and have uncovered a mechanism for cell diversification based on transient transcriptional inputs early in development. Second, we explore what defines the unique properties of specialized cells. Post-transcriptional repression by miRNAs contributes to cell specialization, and we focus on the roles of miRNAs in neuron and muscle diversification. We have found that miRNAs support the unique physiology of some specialized cells by selective repression of otherwise broadly-transcribed, house-keeping genes. To address these questions, we draw from the molecular biology, genetics and RNA biochemistry toolsets. To extract fundamental concepts in cellular differentiation, we use the nematode C. elegans as our primary model system.