Adult Neural Lineages, Transcriptional Trajectories and Gene Programs in the Sea Anemone Nematostella vectensis

Animal tissues are built from specialized cells generated and renewed through cellular lineage decisions. Neural cells are a key animal-specific cell type to coordinate organismal function, with extensive diversity across animals. Some animal lineages, including cnidarians (sea anemones, corals, jellyfish), undergo lifelong renewal of all cell types, including neurons. The genetically tractable sea anemone Nematostella vectensis (Cnidaria, Anthozoa) provides an in vivo system to examine how neural lineages are structured and how distinct neural identities are specified in the context of continuous adult neural renewal. This dissertation investigates the cellular and molecular bases of lifelong neurogenesis in the growing adult. By combining photoconvertible reporter-based pseudo-lineage tracing, single-neuron resolution imaging, and targeted single-cell transcriptomics with recorded lineage status, this work reconstructs the lineage architecture and transcriptional programs underlying adult neurogenesis. This shows that the two main neural cell classes, peptidergic neurons and cnidocytes are generated in a distributed manner alongside the primary body axis, supporting a model of additive distributed neurogenesis rather than spatially restricted neurogenic niches. Newly generated peptidergic neurons are specified proportionally to pre-existing neural subtypes and can be stably integrated into a persistent nerve net architecture. Lineage analyses support that the main neuronal cell class, peptidergic neurons, arises directly from a broadly multipotent progenitor pool. In contrast, cnidarian-specific neural cells, the cnidocytes, develop from a separate cellular lineage, with a lack of a neural-exclusive bipotent progenitor state. At the transcriptional level, peptidergic neurons are specified through a common peptidergic gene regulatory program associated to their shared cellular lineage, combined with subtype-specific modules. Cnidocytes, by contrast, undergo biphasic maturation, in which a late-onset neural program, distinct from that of peptidergic neurons, is secondarily activated. Comparisons across cnidarians support the conservation of this biphasic mode of neural specification and point towards the existence of two largely distinct neural gene programs at the base of Cnidaria. Together, these provide groundwork to understand adult neurogenesis in an anthozoan cnidarian and suggest an early divergence of neural developmental programs associated to lineage architecture, which may have constrained the diversification of neural cell types in early animals.