NvPOU4/Brain3 functions as a terminal selector gene in the nervous system of the cnidarian Nematostella vectensis

Terminal selectors are transcription factors that control the morphological, physiological and molecular features that characterize distinct cell types. Here we use expression analyses and a transgenic reporter line to show that NvPOU4 is expressed in post-mitotic cells that give rise to a diverse set of neural cell types in the sea anemone Nematostella vectensis. We generated a loss-of-function allele by CRISPR/Cas9 and used additional transgenic reporter lines to show that the initial specification of neural cells is not affected in the NvPOU4 mutants. Analyses of transcriptomes derived from the mutants and from different neural cell populations revealed that NvPOU4 is required for the execution of the terminal differentiation program of these neural cells. These findings suggest that POU4 genes have ancient functions as terminal selectors for morphologically and functionally highly disparate types of neurons and they provide experimental support for the relevance of terminal selectors for understanding the evolution of cell types.