CHR3: a <i>Caenorhabditis elegans</i> orphan nuclear hormone receptor required for proper epidermal development and molting

Kostrouchová, Marta; Krause, Michael; Kostrouch, Zdeněk; Rall, J. E.

doi:10.1242/dev.125.9.1617

Cited by 102 publications

(38 citation statements)

References 64 publications

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“…NHR-23 is orthologous to DHR3/Nr1f1, an ecdysone-controlled fly transcription factor important for metamorphosis (Kostrouchova 1998). In metamorphosis, DHR3 activates FTZ-F1 (Ou and King-Jones, 2013), the orthologue of a second one of our screen hits, NHR-25/Nr5a.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we have identified six transcription factors with roles in molting and, potentially, oscillatory gene expression. Validating our approach, we identified NHR-23/Rora, arguably the best characterized molting transcription factor, whose depletion was previously shown to cause a failure of ecdysis and larval arrest (Frand et al, 2005; Gissendanner et al, 2004; Johnson et al, 2021; Kostrouchova et al, 1998; Kostrouchova et al, 2001; Kouns et al, 2011) and a role in regulating collagens and hedgehog-related genes (Kouns et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Validating our approach, we identified NHR-23/Rora, arguably the best characterized molting transcription factor, whose depletion was previously shown to cause a failure of ecdysis and larval arrest (Frand et al, 2005;Gissendanner et al, 2004;Johnson et al, 2021;Kostrouchova et al, 1998;Kostrouchova et al, 2001;Kouns et al, 2011) and a role in regulating collagens and hedgehog-related genes (Kouns et al, 2011). NHR-23 is orthologous to DHR3/Nr1f1, an ecdysone-controlled fly transcription factor important for metamorphosis (Kostrouchova 1998). In metamorphosis, DHR3 activates FTZ-F1 (Ou and King-Jones, 2013), the orthologue of a second one of our screen hits, NHR-25/Nr5a.…”

Section: Discussionmentioning

confidence: 99%

“…We expected mutants with the following phenotypes: i) altered developmental tempo, which could be faster or slower, and specific for a particular oscillation phase or continuously through the cycle, The nuclear hormone receptors NHR-23 and NHR-25 have previously been shown to function in molting (Frand et al, 2005;Gissendanner et al, 2004;Gissendanner and Sluder, 2000;Johnson et al, 2021;Kostrouchova et al, 1998;Kostrouchova et al, 2001), and we and others have described functions of BLMP-1 in oscillatory gene expression and cuticle formation (Hauser et al, 2021;Sandhu et al, 2021;Stec et al, 2021). Here, we sought to establish further the function of GRH-1, first, because we wished to understand whether class III phenotypes can indeed be predictive of clock dysfunction, second, because orthologous Grainyhead(-like) proteins function in epithelial cell fate control and remodeling of epithelial tissues in other animals (Sundararajan et al, 2020), suggesting a potentially conserved function and third, because its function in C. elegans development has remained largely unexplored (Venkatesan et al, 2003).…”

Section: A Targeted Screen Identifies Transcription Factors Involved ...mentioning

confidence: 99%

“…From a set of 92 such transcription factors (Hendriks et al, 2014), we sought to identify those that affected duration of, or progression through, molts. We identified six hits, including the nuclear hormone receptors NHR-23 and NHR-25 that were previously linked to molting (Frand et al, 2005; Gissendanner et al, 2004; Gissendanner and Sluder, 2000; Johnson et al, 2021; Kostrouchova et al, 1998; Kostrouchova et al, 2001). We characterize the function of GRH-1, the sole C. elegans member of the phylogenetically conserved LSF/Grainyhead family (Venkatesan et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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The Grainyhead/LSF transcription factor GRH-1 is rhythmically required for molting

Meeuse

Nahar

Braun

et al. 2022

Preprint

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Molting, that is, the synthesis and shedding of a cuticular exoskeleton, is a defining characteristic of ecdysozoa. In nematodes such as C. elegans, molts rhythmically terminate each of four larval stages. The molting cycle is tightly coupled to the rhythmic expression of thousands of genes. The mechanisms that support the regular molting cycle and oscillatory gene expression have remained largely elusive. Here, we performed an RNAi-based screen for transcription factors required for molting to identify potential components of a molting clock. We find that depletion of GRH-1, BLMP-1, NHR-23, NHR-25, MYRF-1 or BED-3 impairs progression through the molting cycle. We characterize GRH-1, a Grainyhead/LSF transcription factor whose functions in C. elegans development have remained largely unexplored, but whose orthologues in other animals are known to be key epithelial cell fate regulators. We show that GRH-1 depletion causes a dose-dependent extension of molt duration, with severe depletion causing defects in cuticle formation and shedding, and larval death. GRH-1 is required repetitively, during a specific time window prior to each larval molt. This rhythmic activity is consistent with the rhythmic accumulation of GRH-1 protein. These features are consistent with GRH-1 functioning as a key component, or high-level output, of the a gene regulatory network that controls molting. As its mammalian orthologues, as well as those of BLMP-1 and NHR-23, have been implicated in rhythmic homeostatic skin regeneration in mouse, the mechanisms underlying rhythmic C. elegans molting may be conserved beyond nematodes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: A Targeted Screen Identifies Transcription Factors Involved ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Grainyhead/LSF transcription factor GRH-1 is rhythmically required for molting

Meeuse

Nahar

Braun

et al. 2022

Preprint

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Cell proliferation and growth in C. elegans

Lambie

2002

BioEssays

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The cell division and differentiation events that occur during the development of the nematode Caenorhabditis elegans are nearly identical between different individuals, a feature that distinguishes this organism from larger and more complex metazoans, such as humans and Drosophila. In view of this discrepancy, it might be expected that the regulation of cell growth, division and differentiation in C. elegans would involve mechanisms separate from those utilized in larger animals. However, the results of recent genetic, molecular and cellular studies indicate that C. elegans employs an arsenal of developmental regulatory mechanisms quite similar to those wielded by its arthropod and vertebrate relatives. Thus, the nematode system is providing both novel and complementary insights into the general problem of how growth and patterning events are integrated in development. This review offers a general perspective on the regulation of cell division and growth in C. elegans, emphasizing recent studies of these crucial aspects of development.

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Thehedgehog-related genequa-1 is required for molting inCaenorhabditis elegans

et al. 2006

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The Caenorhabditis elegans genome encodes ten proteins that share similarity with Hedgehog through the C-terminal Hint/Hog domain. While most genes are members of larger gene families, qua-1 is a single copy gene. Here we show that orthologs of qua-1 exist in many nematodes, including Brugia malayi, which shared a common ancestor with C. elegans about 300 million years ago. The QUA-1 proteins contain an N-terminal domain, the Qua domain, that is highly conserved, but whose molecular function is not known. We have studied the expression pattern of qua-1 in C. elegans using a qua-1::GFP transcriptional fusion. qua-1 is mainly expressed in hyp1 to hyp11 hypodermal cells, but not in seam cells. It is also expressed in intestinal and rectal cells, sensilla support cells, and the P cell lineage in L1. The expression of qua-1::GFP undergoes cyclical changes during development in phase with the molting cycle. It accumulates prior to molting and disappears between molts. Disruption of the qua-1 gene function through an internal deletion that causes a frame shift with premature stop in the middle of the gene results in strong lethality. The animals arrest in the early larval stages due to defects in molting. Electron microscopy reveals double cuticles due to defective ecdysis, but no obvious defects are seen in the hypodermis. Qua domain-only::GFP and full-length QUA-1::GFP fusion constructs are secreted and associated with the overlying cuticle, but only QUA-1::GFP rescues the mutant phenotype. Our results suggest that both the Hint/Hog domain and Qua domain are critically required for the function of QUA-1.

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CHR3: a Caenorhabditis elegans orphan nuclear hormone receptor required for proper epidermal development and molting

Cited by 102 publications

References 64 publications

The Grainyhead/LSF transcription factor GRH-1 is rhythmically required for molting

The Grainyhead/LSF transcription factor GRH-1 is rhythmically required for molting

Cell proliferation and growth in C. elegans

Thehedgehog-related genequa-1 is required for molting inCaenorhabditis elegans

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