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Title: On building brains and making diverse neurons during whole-body regeneration in the acoel Hofstenia miamia
Abstract: The complexity of the animal nervous system begs the question of how varied neural cell populations are generated. Further, understanding the mechanisms that effectively replace these neural populations in diverse animals provides a comparative framework to understand the evolution of neurogenesis. Most knowledge regarding the patterning and specification of neural populations comes from work focusing on embryonic development; however, limited work has been performed to identify mechanisms underlying the regeneration or re-specification of entire nervous systems within adult animals. Among vertebrates, some animals are capable of replacing select neural cell types and tissues through the use of restricted progenitors. However, none of the current vertebrate models are capable of extensive neural regeneration. Among invertebrates, several animals are capable of whole-body regeneration, i.e., the capacity to replace any missing cell type, including neural cell types. Xenacoelmorpha is a clade thought to be sister to all other bilaterians (or to ambulacrarians) and includes a number of highly regenerative animals. One of these animals, Hofstenia miamia, has been recently established as a model for mechanistic studies of whole-body regeneration. Hofstenia has an organized nervous system and can regenerate all detectable neural cell types through differentiation of its adult pluripotent stem cells, called neoblasts. This makes Hofstenia a promising system to interrogate mechanisms of neural specification and differentiation during whole-body regeneration. Understanding the mechanisms governing neural specification and differentiation in Hofstenia will allow us to make inferences about how adult neurogenesis, and more broadly the nervous system, has evolved among metazoans. In this dissertation, I describe the architecture and regeneration of the Hofstenia nervous system (Chapter 1), identify the heterogeneity of adult pluripotent stem cells and their putative trajectories including neural progenitors (Chapter 2), and determine a gene regulatory network governing early steps of neurogenesis during whole-body regeneration (Chapter 3).
Committee: Mansi Srivastava (Advisor), Gonzalo Giribet, Jessica Whited, Yun Zhang