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 (e.g. the highly specialized physiology of some neurons or muscle cells makes them particularly susceptible to mutations in broadly expressed genes, that do not affect other cell types). 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 neurons and muscle cells that follow different trajectories but later seemingly converge to the same terminal identity. Developmental convergence is widespread in animal development, and we have established models and tools to study the gene-regulatory mechanisms behind two aspects of this phenomenon: i) how do cells from different lineages converge to the same terminal identity, and ii) do convergent cell types carry molecular and functional signatures of their different histories. 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. Moreover, we found that miRNAs support the unique physiology of some specialized cells by selective repression of otherwise broadly-transcribed, house-keeping genes. Such reduced house- keeping function represents a possible source of susceptibilities in specialized cells, which we have been following up in the context of neurons and muscle cells. 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.
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