NvPOU4/Brain3 Functions as a Terminal Selector Gene in the Nervous System of the Cnidarian Nematostella vectensis

Tournière, Océane; Dolan, David; Richards, Gemma S.; Sunagar, Kartik; Columbus-Shenkar, Yaara Y; Moran, Yehu; Rentzsch, Fabian

doi:10.1016/j.celrep.2020.03.031

Cited by 52 publications

(97 citation statements)

References 96 publications

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“…NvNcol3 is also not differentially expressed in mutants. Additionally, transcription factors NvPaxA and NvPou4, which are known regulators of cnidocyte differentiation (52,58), are not differentially expressed in either late planula or primary polyps. In contrast, Cnido-Jun and Cnido-Fos1 are downregulated in mutants at both stages ( Figure S7A).…”

Section: Discussionmentioning

confidence: 95%

“…There are currently no conditional loss-of-function approaches established for Nematostella and we therefore decided to use a cell-type-specific rescue approach. We expressed NvLsd1 under the NvPOU4 promoter that, in the tentacles, is primarily expressed in post-mitotic cnidocytes (52). We generated F0 mosaic transgenics and stained for cnidocytes using NvPOU4::NvHistoneH2B as a control.…”

Section: Nvlsd1 Mutants Have Defects In Cnidocyte Differentiation Butmentioning

confidence: 99%

“…As in other cnidarians, there are three major, morphological cell types in the Nematostella nervous system; sensory cells, ganglionic neurons and cnidocytes; cnidarian specific neural cells also known as stinging cells (48,49). Recent years have seen advances in the understanding of the development of this nervous system, with a focus on transcription factors and signaling pathways (50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62). How chromatin is regulated during neurogenesis and how chromatin modifiers are integrated with cell differentiation in Nematostella is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarianNematostella vectensis

Gahan

Kouzel

Rentzsch

2020

Preprint

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The evolution of multicellularity was accompanied by the emergence of processes to regulate cell fate, identity and differentiation in a robust and faithful manner. Chromatin regulation has emerged as a key process in development and yet its contribution to the evolution of such processes is largely unexplored. Chromatin is regulated by a diverse set of proteins, which themselves are tightly regulated in order to play cell/ tissue-specific functions. Using the cnidarian Nematostella vectensis, a model for basal metazoans, we explore the function of one such chromatin regulator, Lysine specific demethylase 1 (Lsd1). We generated an endogenously tagged allele and show that the expression of NvLsd1 is developmentally regulated and higher in differentiated neural cells than their progenitors. We further show, using a CRISPR/Cas9 generated mutant that loss of NvLsd1 leads to several distinct developmental abnormalities. Strikingly, NvLsd1 loss leads to the almost complete loss of differentiated cnidocytes, cnidarian-specific neural cells, which we show to be the result of a cell-autonomous requirement for NvLsd1. Together this suggests that complex regulation of developmental processes by chromatin modifying proteins predates the split of the cnidarian and bilaterian lineages, approximately 600 million years ago, and may constitute an ancient feature of animal development.

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Section: Discussionmentioning

confidence: 95%

Section: Nvlsd1 Mutants Have Defects In Cnidocyte Differentiation Butmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarianNematostella vectensis

Gahan

Kouzel

Rentzsch

2020

Preprint

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“…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 (Guillemot and Hassan, 2017; Layden et al, 2012; Lloret-Fernández et al, 2018; Poole et al, 2011). HD TFs are involved in many developmental processes and their role in neuron terminal differentiation is also conserved in different animal groups including cnidaria (Babonis and Martindale, 2017; Briscoe et al, 2000; Hobert, 2016; Shirasaki and Pfaff, 2002; Thor et al, 1999; Tournière et al, 2020). Several NHRs, bZIP and ZF TFs are known to regulate neuron-type specification in mammals, such as Couptf1, Nurr1, Tlx and Nr2e3 NHR TFs (Bovetti et al, 2013; Haider et al, 2000; Roy et al, 2004; Zetterström et al, 1997), Nrl, cMaf and Mafb bZIP TFs (Blanchi et al, 2003; Mears et al, 2001; Wende et al, 2012) or Myt1l, Gli1, Sp8, Ctip2, Fezf1/2 ZF TFs (Arlotta et al, 2005; Hynes et al, 1997; Mall et al, 2017; Shimizu et al, 2010; Waclaw et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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

Jimeno-Martín

Sousa

Daroqui

et al. 2020

Preprint

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To search for general principles underlying neuronal regulatory programs we built an RNA interference library against all transcription factors (TFs) encoded in C. elegans genome and systematically screened for specification defects in ten different neuron types of the monoaminergic (MA) superclass. We identified over 90 TFs involved in MA specification, with at least ten different TFs controlling differentiation of each individual neuron type. These TFs belong predominantly to five TF families (HD, bHLH, ZF, bZIP and NHR). Next, focusing on the complexity of terminal differentiation, we identified and functionally characterized the dopaminergic terminal regulatory program. We found that seven TFs from four different families act in a TF collective to provide genetic robustness and to impose a specific gene regulatory signature enriched in the regulatory regions of dopamine effector genes. Our results provide new insights on neuron-type regulatory programs that could help better understand specification and evolution of neuron types.

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“…Neuronal terminal selectors have been described in different metazoan groups including mammals [5,7], although they have been best characterised in C. elegans, where at least a terminal selector is known for 76 out of the 112 different neuronal types [8]. Interestingly, despite numerous examples of TFs acting as terminal selectors, only a small number of TF families are known to act as neuronal terminal selectors from over 50 different families that are present in the C. elegans genome.…”

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confidence: 99%

The transcription factor LAG-1/CSL plays a Notch-independent role in controlling terminal differentiation, fate maintenance, and plasticity of serotonergic chemosensory neurons

et al. 2021

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During development, signal-regulated transcription factors (TFs) act as basal repressors and upon signalling through morphogens or cell-to-cell signalling shift to activators, mediating precise and transient responses. Conversely, at the final steps of neuron specification, terminal selector TFs directly initiate and maintain neuron-type specific gene expression through enduring functions as activators. C. elegans contains 3 types of serotonin synthesising neurons that share the expression of the serotonin biosynthesis pathway genes but not of other effector genes. Here, we find an unconventional role for LAG-1, the signal-regulated TF mediator of the Notch pathway, as terminal selector for the ADF serotonergic chemosensory neuron, but not for other serotonergic neuron types. Regulatory regions of ADF effector genes contain functional LAG-1 binding sites that mediate activation but not basal repression. lag-1 mutants show broad defects in ADF effector genes activation, and LAG-1 is required to maintain ADF cell fate and functions throughout life. Unexpectedly, contrary to reported basal repression state for LAG-1 prior to Notch receptor activation, gene expression activation in the ADF neuron by LAG-1 does not require Notch signalling, demonstrating a default activator state for LAG-1 independent of Notch. We hypothesise that the enduring activity of terminal selectors on target genes required uncoupling LAG-1 activating role from receiving the transient Notch signalling.

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NvPOU4/Brain3 Functions as a Terminal Selector Gene in the Nervous System of the Cnidarian Nematostella vectensis

Cited by 52 publications

References 96 publications

Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarianNematostella vectensis

Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarianNematostella vectensis

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

The transcription factor LAG-1/CSL plays a Notch-independent role in controlling terminal differentiation, fate maintenance, and plasticity of serotonergic chemosensory neurons

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