Seam Cells Research Articles

Gene expression profiling of epidermal cell types in C. elegans using Targeted DamID.

The epidermis of Caenorhabditis elegans is an essential tissue for survival as it contributes to the formation of the cuticle barrier, as well as facilitates developmental progression and animal growth. Most of the epidermis consists of the hyp7 hypodermal syncytium, the nuclei of which are largely generated by the seam cells that exhibit stem cell-like behaviour during development. How the seam cell progenitors differ transcriptionally from the differentiated hypodermis is poorly understood. Here, we introduce Targeted DamID (TaDa) in C. elegans as a method for identifying genes expressed within a tissue of interest without cell isolation. We show that TaDa signal enrichment profiles can be used to identify genes transcribed in the epidermis and use this method to resolve differences in gene expression between the seam cells and the hypodermis. We finally predict and functionally validate new transcription and chromatin factors acting in seam cell development. These findings provide insights into cell-type-specific gene expression profiles likely associated with epidermal cell fate patterning.

Cryptic genetic variation in a heat shock protein modifies the outcome of a mutation affecting epidermal stem cell development in C. elegans

A fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans. We demonstrate that a putative null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in phenotype expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 is sufficient to modify Wnt signalling and seam cell development, highlighting that natural variation in conserved heat shock proteins can shape phenotype expressivity.

Phenotypic Robustness of Epidermal Stem Cell Number in C. elegans Is Modulated by the Activity of the Conserved N-acetyltransferase nath-10/NAT10.

Individual cells and organisms experience perturbations from internal and external sources, yet manage to buffer these to produce consistent phenotypes, a property known as robustness. While phenotypic robustness has often been examined in unicellular organisms, it has not been sufficiently studied in multicellular animals. Here, we investigate phenotypic robustness in Caenorhabditis elegans seam cells. Seam cells are stem cell-like epithelial cells along the lateral edges of the animal, which go through asymmetric and symmetric divisions contributing cells to the hypodermis and neurons, while replenishing the stem cell reservoir. The terminal number of seam cells is almost invariant in the wild-type population, allowing the investigation of how developmental precision is achieved. We report here that a loss-of-function mutation in the highly conserved N-acetyltransferase nath-10/NAT10 increases seam cell number variance in the isogenic population. RNA-seq analysis revealed increased levels of mRNA transcript variability in nath-10 mutant populations, which may have an impact on the phenotypic variability observed. Furthermore, we found disruption of Wnt signaling upon perturbing nath-10 function, as evidenced by changes in POP-1/TCF nuclear distribution and ectopic activation of its GATA transcription factor target egl-18. These results highlight that NATH-10/NAT-10 can influence phenotypic variability partly through modulation of the Wnt signaling pathway.

A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

Developmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise. We focus here on a population of epidermal cells, the seam cells, which show stem cell-like behaviour and divide symmetrically and asymmetrically over post-embryonic development to generate epidermal and neuronal tissues. We have conducted a mutagenesis screen to identify mutants that introduce phenotypic variability in the normally invariant seam cell population. We report here that a null mutation in the fusogen eff-1 increases seam cell number variability. Using time-lapse microscopy and single molecule fluorescence hybridisation, we find that seam cell division and differentiation patterns are mostly unperturbed in eff-1 mutants, indicating that cell fusion is uncoupled from the cell differentiation programme. Nevertheless, seam cell losses due to the inappropriate differentiation of both daughter cells following division, as well as seam cell gains through symmetric divisions towards the seam cell fate were observed at low frequency. We show that these stochastic errors likely arise through accumulation of defects interrupting the continuity of the seam and changing seam cell shape, highlighting the role of tissue homeostasis in suppressing phenotypic variability during development.

Sjögren Syndrome antigen B regulates LIN28-let-7 axis in Caenorhabditis elegans and human

LIN28 protein and let-7 family micro RNAs (miRNAs) that are an evolutionarily conserved from nematodes to humans are the important regulators of developmental timing by dynamically interacting with each other. However, regulators of LIN28 remain largely elusive. Here, we show the evidences that Sjögren Syndrome antigen B (SSB) protein associates and cooperates with LIN28A and LIN28B, mammalian orthologues of Caenorhabditis elegans lin-28, proteins in the nucleus. Knockdown of SSB in HEK293 cell line resulted in the decrease of the amount of LIN28B mRNAs and proteins, and the increase of the level of mature let-7 miRNAs. Furthermore, RNA interference of ssb-1 gene, a worm SSB orthologue, was sufficient to cause a heterochronic defect in seam cells of C. elegans, recapitulating the phenotype of lin-28 downregulation. Collectively, we suggest that SSB is an important regulator for the LIN28-let-7 axis.

An expanded auxin-inducible degron toolkit for Caenorhabditis elegans.

The auxin-inducible degron (AID) system has emerged as a powerful tool to conditionally deplete proteins in a range of organisms and cell types. Here, we describe a toolkit to augment the use of the AID system in Caenorhabditis elegans. We have generated a set of single-copy, tissue-specific (germline, intestine, neuron, muscle, pharynx, hypodermis, seam cell, anchor cell) and pan-somatic TIR1-expressing strains carrying a co-expressed blue fluorescent reporter to enable use of both red and green channels in experiments. These transgenes are inserted into commonly used, well-characterized genetic loci. We confirmed that our TIR1-expressing strains produce the expected depletion phenotype for several nuclear and cytoplasmic AID-tagged endogenous substrates. We have also constructed a set of plasmids for constructing repair templates to generate fluorescent protein::AID fusions through CRISPR/Cas9-mediated genome editing. These plasmids are compatible with commonly used genome editing approaches in the C. elegans community (Gibson or SapTrap assembly of plasmid repair templates or PCR-derived linear repair templates). Together these reagents will complement existing TIR1 strains and facilitate rapid and high-throughput fluorescent protein::AID tagging of genes. This battery of new TIR1-expressing strains and modular, efficient cloning vectors serves as a platform for straightforward assembly of CRISPR/Cas9 repair templates for conditional protein depletion.

Widespread gpa-4 promoter-driven expression during Caenorhabditis elegans development.

The gpa-4 promoter-driven expression is described as specific for ASIL and ASIR chemosensory neurons in the nematode Caenorhabditis elegans, yet this was mostly examined in adult animals. Here we used a recombination-mediated reporter to test the previously used gpa-4 promoter expression. This reporter highlights all cells in which the gpa-4 promoter has been active at one point or another during development. We show that the gpa-4 promoter is indeed active in ASI, yet to our surprise, thispromoter drives also expression in many other cell types, including the somatic gonad, the seam cells, a subset of tail and head neurons, and muscle cells, demonstrating a widespread activity of this transgenic gpa-4 promoter during embryonic and post-embryonic development.

Rapid determination of nematode cell and organ susceptibility to toxic treatments

In research focused on the intestine of parasitic nematodes, we recently identified small molecule inhibitors toxic to intestinal cells of larval Ascaris suum (nematode intestinal toxins/toxicants; “NITs”). Some NITs had anthelmintic activity across the phylogenetic diversity of the Nematoda. The whole-worm motility inhibition assay quantified anthelmintic activity, but worm responses to NITs in relation to pathology or affected molecular pathways was not acquired. In this study we extended this research to more comprehensively determine in whole larval A. suum the cells, organ systems, molecular targets, and potential cellular pathways involved in mechanisms of toxicity leading to cell death. The experimental system utilized fluorescent nuclear probes (bisbenzimide, propidium iodide), NITs, an A. suum larval parasite culture system and transcriptional responses (RNA-seq) to NITs. The approach provides for rapid resolution of NIT-induced cell death among organ systems (e.g. intestine, excretory, esophagus, hypodermis and seam cells, and nervous), discriminates among NITs based on cell death profiles, and identifies cells and organ systems with the greatest NIT sensitivity (e.g. intestine and apparent neuronal cells adjacent to the nerve ring). Application was extended to identify cells and organs sensitive to several existing anthelmintics. This approach also resolved intestinal cell death and irreparable damage induced in adult A. suum by two NITs, establishing a new model to elucidate relevant pathologic mechanisms in adult worms. RNA-seq analysis resolved A. suum genes responsive to treatments with three NITs, identifying dihydroorotate dehydrogenase (uridine synthesis) and RAB GTPase(s) (vesicle transport) as potential targets/pathways leading to cell death. A set of genes induced by all three NITs tested suggest common stress or survival responses activated by NITs. Beyond the presented specific lines of research, elements of the overall experimental system presented in this study have broad application toward systematic development of new anthelmintics.

Cellular and developmental basis of orofacial clefts

During craniofacial development, defective growth and fusion of the upper lip and/or palate can cause orofacial clefts (OFCs), which are among the most common structural birth defects in humans. The developmental basis of OFCs includes morphogenesis of the upper lip, primary palate, secondary palate, and other orofacial structures, each consisting of diverse cell types originating from all three germ layers: the ectoderm, mesoderm, and endoderm. Cranial neural crest cells and orofacial epithelial cells are two major cell types that interact with various cell lineages and play key roles in orofacial development. The cellular basis of OFCs involves defective execution in any one or several of the following processes: neural crest induction, epithelial-mesenchymal transition, migration, proliferation, differentiation, apoptosis, primary cilia formation and its signaling transduction, epithelial seam formation and disappearance, periderm formation and peeling, convergence and extrusion of palatal epithelial seam cells, cell adhesion, cytoskeleton dynamics, and extracellular matrix function. The latest cellular and developmental findings may provide a basis for better understanding of the underlying genetic, epigenetic, environmental, and molecular mechanisms of OFCs.

5'-Hydroxy-6, 7, 8, 3', 4'-pentamethoxyflavone extends longevity mediated by DR-induced autophagy and oxidative stress resistance in C. elegans.

5'-Hydroxy-6, 7, 8, 3', 4'-pentamethoxyflavone (5-HPF), a polymethoxyflavone compound found in dikamali gum, has been shown to exert a range of beneficial effects on health. We have previously reported that 5-HPF improves the cholinergic dysfunction and also possesses antioxidant properties in Caenorhabditis elegans. In this study, we have identified the effect of 5-HPF on the worm lifespan and its underlying molecular mechanisms. Out of the five tested pharmacological doses of 5-HPF, viz. 6.25, 12.5, 25, 50, and 100μM, the 50μM dose maximally extended the mean life of C. elegans by 28%. The present study revealed that 5-HPF supplementation leads to dietary restriction (DR)-like effects in the worms without altering bacterial metabolism. The analysis of mutant animals fed with 5-HPF suggested that the extended lifespan of C. elegans depends upon multiple DR-related signaling pathways, with NRF2 and FOXA being critical factors. Further investigation into the mechanistic aspects indicated that 5-HPF utilizes autophagy pathway induced by DR through the upregulation of autophagy genes bec-1 and lgg-1, evident from the increase in autophagic puncta in the seam cells of lgg-1::gfp tagged worms. This study identifies the longevity-promoting activity of 5-HPF in C. elegans regulated by oxidative stress-resistance genes and DR-induced autophagy pathway.

A Cell Fate Switch in the Caenorhabditis elegans Seam Cell Lineage Occurs Through Modulation of the Wnt Asymmetry Pathway in Response to Temperature Increase.

Populations often display consistent developmental phenotypes across individuals despite inevitable biological stochasticity. Nevertheless, developmental robustness has limits, and systems can fail upon change in the environment or the genetic background. We use here the seam cells, a population of epidermal stem cells in Caenorhabditis elegans, to study the influence of temperature change and genetic variation on cell fate. Seam cell development has mostly been studied so far in the laboratory reference strain (N2), grown at 20° temperature. We demonstrate that an increase in culture temperature to 25° introduces variability in the wild-type seam cell lineage, with a proportion of animals showing an increase in seam cell number. We map this increase to lineage-specific symmetrization events of normally asymmetric cell divisions at the fourth larval stage, leading to the retention of seam cell fate in both daughter cells. Using genetics and single-molecule imaging, we demonstrate that this symmetrization occurs via changes in the Wnt asymmetry pathway, leading to aberrant Wnt target activation in anterior cell daughters. We find that intrinsic differences in the Wnt asymmetry pathway already exist between seam cells at 20° and this may sensitize cells toward a cell fate switch at increased temperature. Finally, we demonstrate that wild isolates of C. elegans display variation in seam cell sensitivity to increased culture temperature, although their average seam cell number is comparable at 20°. Our results highlight how temperature can modulate cell fate decisions in an invertebrate model of stem cell patterning.

Caudal-dependent cell positioning directs morphogenesis of the C. elegans ventral epidermis

Strikingly, epithelial morphogenesis remains incomplete at the end of C. elegans embryonic development; newly hatched larvae undergo extensive remodelling of their ventral epidermis during the first larval stage (L1), when newly-born epidermal cells move ventrally to complete the epidermal syncytium. Prior to this remodelling, undivided lateral seam cells produce anterior adherens junction processes that are inherited by the anterior daughter cells following an asymmetric division during L1. These adherens junction processes provide the ventral migratory route for these anterior daughters. Here, we show that these processes are perturbed in pal-1/caudal mutant animals, resulting in their inheritance by posterior, seam-fated daughters. This causes aberrant migration of seam daughter cells, disrupting the ventral epidermis. Using 4D-lineaging, we demonstrate that this larval epidermal morphogenesis defect in pal-1 mutants can be traced directly back to an initial cell positioning defect in the embryo. pal-1 expression, driven by a single intronic enhancer, is required to correctly position the seam cells in embryos such that the appropriate cell junctions support the correct migratory paths of seam daughters later in development, irrespective of their fate. Thus, during ventral epithelial remodelling in C. elegans, we show that the position of migrating cells, specified by pal-1/caudal, appears to be more important than their fate in driving morphogenesis.

C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells.

ABSTRACTA correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight into the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by divergent canonical Wnt/β-catenin signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy we observed that symmetric cell divisions maintain asymmetric localization of Wnt/β-catenin pathway components. Our observations, based on lineage-specific knockout and GFP-tagging of endogenous pop-1, support the model that POP-1TCF induces differentiation at a high nuclear level, whereas low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator RNT-1Runx and cofactor BRO-1CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, we found that conserved Runx/CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression.

Role of PRY-1/Axin in heterochronic miRNA-mediated seam cell development

BackgroundCaenorhabditis elegans seam cells serve as a good model to understand how genes and signaling pathways interact to control asymmetric cell fates. The stage-specific pattern of seam cell division is coordinated by a genetic network that includes WNT asymmetry pathway components WRM-1, LIT-1, and POP-1, as well as heterochronic microRNAs (miRNAs) and their downstream targets. Mutations in pry-1, a negative regulator of WNT signaling that belongs to the Axin family, were shown to cause seam cell defects; however, the mechanism of PRY-1 action and its interactions with miRNAs remain unclear.ResultsWe found that pry-1 mutants in C. elegans exhibit seam cell, cuticle, and alae defects. To examine this further, a miRNA transcriptome analysis was carried out, which showed that let-7 (miR-48, miR-84, miR-241) and lin-4 (lin-4, miR-237) family members were upregulated in the absence of pry-1 function. Similar phenotypes and patterns of miRNA overexpression were also observed in C. briggsae pry-1 mutants, a species that is closely related to C. elegans. RNA interference-mediated silencing of wrm-1 and lit-1 in the C. elegans pry-1 mutants rescued the seam cell defect, whereas pop-1 silencing enhanced the phenotype, suggesting that all three proteins are likely important for PRY-1 function in seam cells. We also found that these miRNAs were overexpressed in pop-1 hypomorphic animals, suggesting that PRY-1 may be required for POP-1-mediated miRNA suppression. Analysis of the let-7 and lin-4-family heterochronic targets, lin-28 and hbl-1, showed that both genes were significantly downregulated in pry-1 mutants, and furthermore, lin-28 silencing reduced the number of seam cells in mutant animals.ConclusionsOur results show that PRY-1 plays a conserved role to maintain normal expression of heterochronic miRNAs in nematodes. Furthermore, we demonstrated that PRY-1 acts upstream of the WNT asymmetry pathway components WRM-1, LIT-1, and POP-1, and miRNA target genes in seam cell development.

Medial epithelial seam cell migration during palatal fusion.

The mammalian secondary palate forms from two shelves of mesenchyme sheathed in a single-layered epithelium. These shelves meet during embryogenesis to form the midline epithelial seam (MES). Failure of MES degradation prevents mesenchymal confluence and results in a cleft palate. Previous studies indicated that MES cells undergo features of epithelial-to-mesenchymal transition (EMT) and may become migratory as part of the fusion mechanism. To detect MES cell movement over the course of fusion, we imaged the midline of fusing embryonic ephrin-B2/GFP mouse palates in real time using two-photon microscopy. These mice express an ephrin-B2-driven green fluorescent protein (GFP) that labels the palatal epithelium nuclei and persists in those cells through the time window necessary for fusion. We observed collective migration of MES cells toward the oral surface of the palatal shelf over 48 hr of imaging, and we confirmed histologically that the imaged palates had fused by the end of the imaged period. We previously reported that ephrin reverse signaling in the MES is required for palatal fusion. We therefore added recombinant EphA4/Fc protein to block this signaling in imaged palates. The blockage inhibited fusion, as expected, but did not change the observed migration of GFP-labeled cells. Thus, we uncoupled migration and fusion. Our data reveal that palatal MES cells undergo a collective, unidirectional movement during palatal fusion and that ephrin reverse signaling, though required for fusion, controls aspects of the fusion mechanism independent of migration.

HSP-4/BiP expression in secretory cells is regulated by a developmental program and not by the unfolded protein response.

Differentiation of secretory cells leads to sharp increases in protein synthesis, challenging endoplasmic reticulum (ER) proteostasis. Anticipatory activation of the unfolded protein response (UPR) prepares cells for the onset of secretory function by expanding the ER size and folding capacity. How cells ensure that the repertoire of induced chaperones matches their postdifferentiation folding needs is not well understood. We find that during differentiation of stem-like seam cells, a typical UPR target, the Caenorhabditis elegans immunoglobulin heavy chain-binding protein (BiP) homologue Heat-Shock Protein 4 (HSP-4), is selectively induced in alae-secreting daughter cells but is repressed in hypodermal daughter cells. Surprisingly, this lineage-dependent induction bypasses the requirement for UPR signaling. Instead, its induction in alae-secreting cells is controlled by a specific developmental program, while its repression in the hypodermal-fated cells requires a transcriptional regulator B-Lymphocyte–Induced Maturation Protein 1 (BLMP-1/BLIMP1), involved in differentiation of mammalian secretory cells. The HSP-4 induction is anticipatory and is required for the integrity of secreted alae. Thus, differentiation programs can directly control a broad-specificity chaperone that is normally stress dependent to ensure the integrity of secreted proteins.

Convergent evolution of saccate body shapes in nematodes through distinct developmental mechanisms

BackgroundThe vast majority of nematode species have vermiform (worm-shaped) body plans throughout post-embryonic development. However, atypical body shapes have evolved multiple times. The plant-parasitic Tylenchomorpha nematode Heterodera glycines hatches as a vermiform infective juvenile. Following infection and the establishment of a feeding site, H. glycines grows disproportionately greater in width than length, developing into a saccate adult. Body size in Caenorhabditis elegans was previously shown to correlate with post-embryonic divisions of laterally positioned stem cell-like ‘seam’ cells and endoreduplication of seam cell epidermal daughters. To test if a similar mechanism produces the unusual body shape of saccate parasitic nematodes, we compared seam cell development and epidermal ploidy levels of H. glycines to C. elegans. To study the evolution of body shape development, we examined seam cell development of four additional Tylenchomorpha species with vermiform or saccate body shapes.ResultsWe confirmed the presence of seam cell homologs and their proliferation in H. glycines. This results in the adult female epidermis having approximately 1800 nuclei compared with the 139 nuclei in the primary epidermal syncytium of C. elegans. Similar to C. elegans, we found a significant correlation between H. glycines body volume and the number and ploidy level of epidermal nuclei. While we found that the seam cells also proliferate in the independently evolved saccate nematode Meloidogyne incognita following infection, the division pattern differed substantially from that seen in H. glycines. Interestingly, the close relative of H. glycines, Rotylenchulus reniformis does not undergo extensive seam cell proliferation during its development into a saccate form.ConclusionsOur data reveal that seam cell proliferation and epidermal nuclear ploidy correlate with growth in H. glycines. Our finding of distinct seam cell division patterns in the independently evolved saccate species M. incognita and H. glycines is suggestive of parallel evolution of saccate forms. The lack of seam cell proliferation in R. reniformis demonstrates that seam cell proliferation and endoreduplication are not strictly required for increased body volume and atypical body shape. We speculate that R. reniformis may serve as an extant transitional model for the evolution of saccate body shape.

DnaJ chaperones contribute to canalization.

Canalization, an intrinsic robustness of development to external (environmental) or internal (genetic) perturbations, was first proposed over half a century ago. However, whether the robustness to environmental stress (environmental canalization [EC]) and to genetic variation (genetic canalization) are underpinned by the same molecular basis remains elusive. The recent discovery of the involvement of two endoplasmic reticulum (ER)-associated DnaJ genes in developmental buffering, orthologues of which are conserved across Metazoa, indicates that the role of ER-associated DnaJ genes might be conserved across the animal kingdom. To test this, we surveyed the ER-associated DnaJ chaperones in the nematode Caenorhabditis elegans. We then quantified the phenotype, in the form of variance and mean of seam cell counts, from RNA interference knockdown of DnaJs under three different temperatures. We find that seven out of eight ER-associated DnaJs are involved in either EC or microenvironmental canalization. Moreover, we also found two DnaJ genes not specifically associated with ER (DNAJC2/dnj-11 and DNAJA2/dnj-19) were involved in canalization. Protein expression pattern showed that these DnaJs are upregulated by heat stress, yet not all of them are expressed in the seam cells. Moreover, we found that most of the buffering DnaJs also control lifespan. We therefore concluded that a number of DnaJ chaperones, not limited to those associated with the ER, are involved in canalization as a part of the complex system that underlies development.

Heterochronic Phenotype Analysis of Hypodermal Seam Cells in Caenorhabditis elegans.

Heterochrony refers to changes in the timing of developmental events, and it is precisely regulated in the organisms by the heterochronic genes such as C. elegans lin-4 and let-7. Mutations in these genes cause precocious or retarded development of certain cell lineages. With well-defined cell lineages, C. elegans is one of the best model systems to study heterochronic genes, since the subtle changes in the development of cell lineages can be easily identified. Among the different cell types in C. elegans, hypodermal seam cells and their lineages are well known to be maintained by lin-14, whose expression level is regulated by two miRNA genes, lin-4 and let-7, at the larval stages. Therefore, analyzing the heterochronic phenotype of hypodermal seam cells in C. elegans could yield detailed insights into the status of the miRNA pathway. Here we describe the assay protocol to analyze the heterochronic phenotypes of C. elegans hypodermal seam cells, which can be used as a reliable method to study the miRNA pathway.

Epidermal Remodeling in Caenorhabditis elegans Dauers Requires the Nidogen Domain Protein DEX-1.

Phenotypic plasticity is a critical component of an organism’s ability to thrive in a changing environment. The free-living nematode Caenorhabditis elegans adapts to unfavorable environmental conditions by pausing reproductive development and entering a stress-resistant larval stage known as dauer. The transition into dauer is marked by vast morphological changes, including remodeling of epidermis, neurons, and muscle. Although many of these dauer-specific traits have been described, the molecular basis of dauer-specific remodeling is still poorly understood. Here we show that the nidogen domain-containing protein DEX-1 facilitates stage-specific tissue remodeling during dauer morphogenesis. DEX-1 was previously shown to regulate sensory dendrite formation during embryogenesis. We find that DEX-1 is also required for proper remodeling of the stem cell-like epidermal seam cells. dex-1 mutant dauers lack distinct lateral cuticular alae during dauer and have increased sensitivity to sodium dodecyl sulfate. Furthermore, we find that DEX-1 is required for proper dauer mobility. We show that DEX-1 is secreted from the seam cells during dauer, but acts locally in a cell-autonomous manner. We find that dex-1 expression during dauer is regulated through DAF-16/FOXO–mediated transcriptional activation. Finally, we show that dex-1 acts with a family of zona pellucida domain-encoding genes to regulate dauer-specific epidermal remodeling. Taken together, our data indicate that DEX-1 is an extracellular matrix component that plays a central role in C. elegans epidermal remodeling during dauer.