NvPOU4/Brain3functions as a terminal selector gene in the nervous system of the cnidarianNematostella vectensis

Abstract

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.

Control of spinal motor neuron terminal differentiation through sustained Hoxc8 gene activity

“…Numerous genetic studies in the nematode C. elegans support the idea that continuously expressed TFs (termed “terminal selectors”) establish during development and maintain throughout postembryonic life the identity and function of individual neuron types by activating the expression of terminal differentiation genes (e.g., NT biosynthesis components, ion channels, adhesion and signaling molecules)(Deneris and Hobert, 2014, Hobert, 2008, Hobert, 2016). Multiple cases of terminal selectors for various neuron types have already been described in flies, cnidarians, marine chordates, and mice, suggesting deep conservation for this type of regulators(Allan and Thor, 2015, Deneris and Hobert, 2014, Hobert, 2008, Hobert, 2016, Hobert and Kratsios, 2019, Tourniere et al, 2020). However, it remains unclear whether spinal MNs in vertebrates employ a terminal selector-type of mechanism to acquire and maintain their terminal differentiation features.…”

The genetic basis for PRC1 complex diversity emerged early in animal evolution

“…Of the two PCGF5 paralogs in Nematostella, NvPCGF5a is highly expressed in the nervous system based on our analysis. In addition, both Nematostella NvPCGF5a and NvPCGF5b are found to be upregulated in NvElav1 + neurons at later developmental stages (81). This is striking as, in mammals, PCGF5 is also highly expressed in the neural progenitors (56,72) and has been shown to play important functions both during neural differentiation and in the adult nervous system (55,56).…”

Joint actions of diverse transcription factor families establish neuron-type identities and promote enhancer selectivity

“…The ancestral role of bHLH TFs as proneural factors has been established in a wide range of metazoans including vertebrates, Drosophila, C. elegans and the cnidaria Nematostella vectensis which has one of the most simple nervous systems (Poole et al 2011; Lloret-Fernández et al 2018; Guillemot and Hassan 2017; Layden et al 2012). HD TFs are involved in many developmental processes and their role in neuron terminal differentiation is also conserved in different animal groups including cnidaria (Hobert 2016; Thor et al 1999; Tournière et al 2020; Babonis and Martindale 2017; Briscoe et al 2000; Shirasaki and Pfaff 2002). Interestingly, our results suggest HD functions are not limited to neuron terminal differentiation but do also play important roles as lineage determinants.…”