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 of entire nervous systems within adult animals. Vertebrates are capable of replacing select neural cell types through the use of restricted progenitors; however, none of the current models are capable of whole brain¬ regeneration. Several invertebrates 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 a sister group to all other bilaterians and includes a number of highly regenerative animals. One of these animals, Hofstenia miamia, has been established as a model for mechanistic studies of whole-body regeneration. H. miamia has an organized nervous system and can regenerate all detectable neural cell types through differentiation of its adult pluripotent stem cells. This makes H. miamia a promising system to interrogate mechanisms of neural specification and differentiation during whole-body regeneration as well as their evolution. In this dissertation, I describe the architecture and regeneration of the H. miamia 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 the early steps of neurogenesis during whole-body regeneration (Chapter 3).