Cnidarian hair cell development illuminates an ancient role for the class IV POU transcription factor in defining mechanoreceptor identity

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    Evaluation Summary:

    This manuscript focusses on a little studied, but highly interesting presumptive mechanosensory cell type in cnidarians, the 'hair cell'. The work shows that the POU-IV transcription factor is required for the maturation of this cell type in the sea anemone Nematostella vectensis. Because POU-IV transcription factors also play essential roles in the differentiation of mechanoreceptors in many bilaterian phyla, this suggests an evolutionarily ancient role of POU-IV in regulating mechanosensory identity. This study will hence be of great interest to developmental biologists and evolutionary biologists who are interested in the developmental evolution of neuronal cell types.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

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Abstract

Although specialized mechanosensory cells are found across animal phylogeny, early evolutionary histories of mechanoreceptor development remain enigmatic. Cnidaria (e.g. sea anemones and jellyfishes) is the sister group to well-studied Bilateria (e.g. flies and vertebrates), and has two mechanosensory cell types – a lineage-specific sensory effector known as the cnidocyte, and a classical mechanosensory neuron referred to as the hair cell. While developmental genetics of cnidocytes is increasingly understood, genes essential for cnidarian hair cell development are unknown. Here, we show that the class IV POU homeodomain transcription factor (POU-IV) – an indispensable regulator of mechanosensory cell differentiation in Bilateria and cnidocyte differentiation in Cnidaria – controls hair cell development in the sea anemone cnidarian Nematostella vectensis. N. vectensis POU-IV is postmitotically expressed in tentacular hair cells, and is necessary for development of the apical mechanosensory apparatus, but not of neurites, in hair cells. Moreover, it binds to deeply conserved DNA recognition elements, and turns on a unique set of effector genes – including the transmembrane receptor-encoding gene polycystin 1 – specifically in hair cells. Our results suggest that POU-IV directs differentiation of cnidarian hair cells and cnidocytes via distinct gene regulatory mechanisms, and support an evolutionarily ancient role for POU-IV in defining the mature state of mechanosensory neurons.

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  1. Author Response:

    Reviewer #1:

    The paper demonstrates the role of Pou domains for various sensory cells. Using CRISPR to delete the gene, the authors show an incomplete deletion of sensory cells. Further evidence shows problems with the formation of mechanosensory cells. Overall, the presentation is clear but can be expanded by adding the role of bHLH genes (Atoh1 is upstream of Pou4f3). If possible, I suggest expanding the role of TMC as it is the main receptor in mammalian hair cells that connects to the stereocilia. Please note that the cnidarian organization is a central kinocilium surrounded by microvilli, comparable to choanoflagellates. This paper is a great original presentation but it could provide a broader perspective by expanding on the evolution of Pou IV and by adding a discussion of the evolution of bHLH, Myc and TMC …

  2. Evaluation Summary:

    This manuscript focusses on a little studied, but highly interesting presumptive mechanosensory cell type in cnidarians, the 'hair cell'. The work shows that the POU-IV transcription factor is required for the maturation of this cell type in the sea anemone Nematostella vectensis. Because POU-IV transcription factors also play essential roles in the differentiation of mechanoreceptors in many bilaterian phyla, this suggests an evolutionarily ancient role of POU-IV in regulating mechanosensory identity. This study will hence be of great interest to developmental biologists and evolutionary biologists who are interested in the developmental evolution of neuronal cell types.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with …

  3. Reviewer #1 (Public review)

    The paper demonstrates the role of Pou domains for various sensory cells. Using CRISPR to delete the gene, the authors show an incomplete deletion of sensory cells. Further evidence shows problems with the formation of mechanosensory cells.
    Overall, the presentation is clear but can be expanded by adding the role of bHLH genes (Atoh1 is upstream of Pou4f3). If possible, I suggest expanding the role of TMC as it is the main receptor in mammalian hair cells that connects to the stereocilia. Please note that the cnidarian organization is a central kinocilium surrounded by microvilli, comparable to choanoflagellates. This paper is a great original presentation but it could provide a broader perspective by expanding on the evolution of Pou IV and by adding a discussion of the evolution of bHLH, Myc and TMC in …

  4. Reviewer #2 (Public Review):

    Whereas the role of POU-IV for the differentiation of cnidocytes and other neurons of Nematostella has been previously characterized (Tourniere et al., 2020), the present study extends previous reports by specifically addressing the role of POU-IV for the so-called "hair cells" of Nematostella (not to be confused with the hair cells of the vertebrate inner ear and lateral line). These presumably mechanosensory hair cells are identified here as postmitotic neurons, which are ciliated and carry a collar of stereovilli - actin-filled microvilli with a long actin-rich rootlet. Using CRISPR/Cas9 based gene editing, the study shows that transgenic animals, in which the POU-IV gene has been disrupted, become touch insensitive. While hair cells can still be identified in these POU-IV mutants, they lack the …

  5. Reviewer #3 (Public Review):

    In this manuscript, Ozmet et al. investigated the developmental genetics of mechanoreceptor cells (hair cells) in the cnidarian model N. vectensis. They used CRISPR-Cas9-mediated mutagenesis to showed that POU-IV homeodomain transcription factor regulates the differentiation of hair cells in this organism. The authors applied behavior assay, EM observations, and various types of fluorescence labeling to show that pou-iv -/- polyps exhibit defects in touch-sensitive behavior, likely due to the failure of forming the complete stereocilliary rootlet structure near the apical side of the hair cells in those mutant polyps. The authors went on to apply ChIP-seq in N. vectensis and showed that the POU-IV-binding motifs are conserved across Cnidaria and Bilateria. They also used this ChIP-seq dataset to screen for …