Christina L Greene, Geoffrey Traeger, Akshay Venkatesh, David Han, Mark W Majesky
{"title":"Origins of Aortic Coarctation: A Vascular Smooth Muscle Compartment Boundary Model.","authors":"Christina L Greene, Geoffrey Traeger, Akshay Venkatesh, David Han, Mark W Majesky","doi":"10.3390/jdb13020013","DOIUrl":"https://doi.org/10.3390/jdb13020013","url":null,"abstract":"<p><p>Compartment boundaries divide the embryo into segments with distinct fates and functions. In the vascular system, compartment boundaries organize endothelial cells into arteries, capillaries, and veins that are the fundamental units of a circulatory network. For vascular smooth muscle cells (SMCs), such boundaries produce mosaic patterns of investment based on embryonic origins with important implications for the non-uniform distribution of vascular disease later in life. The morphogenesis of blood vessels requires vascular cell movements within compartments as highly-sensitive responses to changes in fluid flow shear stress and wall strain. These movements underline the remodeling of primitive plexuses, expansion of lumen diameters, regression of unused vessels, and building of multilayered artery walls. Although the loss of endothelial compartment boundaries can produce arterial-venous malformations, little is known about the consequences of mislocalization or the failure to form SMC-origin-specific boundaries during vascular development. We propose that the failure to establish a normal compartment boundary between cardiac neural-crest-derived SMCs of the 6th pharyngeal arch artery (future ductus arteriosus) and paraxial-mesoderm-derived SMCs of the dorsal aorta in mid-gestation embryos leads to aortic coarctation observed at birth. This model raises new questions about the effects of fluid flow dynamics on SMC investment and the formation of SMC compartment borders during pharyngeal arch artery remodeling and vascular development.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 2","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Activation of Marck-like Genes and Proteins During Initial Phases of Regeneration in the Amputated Tail and Limb of the Lizard <i>Podarcis muralis</i>.","authors":"Lorenzo Alibardi","doi":"10.3390/jdb13020012","DOIUrl":"https://doi.org/10.3390/jdb13020012","url":null,"abstract":"<p><p>Molecules involved in the activation of regeneration in reptiles are almost unknown. MARCK-like proteins are indicated to activate regeneration in some amphibians and fish, and it would be important to know whether this is a general process also present in other vertebrates. To address this problem, the present study reports the immunolocalization of a MARCK-like protein in injured tissues of a lizard. Bioinformatics and immunofluorescence after 5BrdU administration, and detection of MARCK-like proteins, have been performed on regenerating tail and limb of the lizard <i>Podarcis muralis</i>. Transcriptome data indicate up-regulation of MARCKS and MARCK-like1 expression in the initial regenerating tail and limb blastemas, supporting their involvement in the activation of regeneration in both appendages. Immunofluorescence for 5BrdU shows numerous proliferating cells in the blastemas of both appendages. Immunolocalization of a MARCK-like protein, using an antibody generated against a homologous protein from the axolotl, shows that the wound epidermis, nerves, and myotubes accumulate most of the protein in the limb and tail. MARCK-like immunolabeling is also detected in the regenerating spinal cord of the tail. The study indicates that, although the limb later turns into a scar, the MARCK-like protein is also up-regulated in this appendage, like in the regenerating tail. These results indicate that the initial reaction to an injury in lizards, an amniote representative, includes some triggering processes observed in amphibians and fish (anamniotes), with the activation of MARCK-like genes and proteins. This suggests that a MARCK-like-dependant mechanism for tissue repair is likely activated during the initial phases of vertebrate wound healing.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 2","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gracy X Rosario, Samuel Brown, Subhradip Karmakar, Mohammad A Karim Rumi, Nihar R Nayak
{"title":"Super-Enhancers in Placental Development and Diseases.","authors":"Gracy X Rosario, Samuel Brown, Subhradip Karmakar, Mohammad A Karim Rumi, Nihar R Nayak","doi":"10.3390/jdb13020011","DOIUrl":"https://doi.org/10.3390/jdb13020011","url":null,"abstract":"<p><p>The proliferation of trophoblast stem (TS) cells and their differentiation into multiple lineages are pivotal for placental development and functions. Various transcription factors (TFs), such as CDX2, EOMES, GATA3, TFAP2C, and TEAD4, along with their binding sites and cis-regulatory elements, have been studied for their roles in trophoblast cells. While previous studies have primarily focused on individual enhancer regions in trophoblast development and differentiation, recent attention has shifted towards investigating the role of super-enhancers (SEs) in different trophoblast cell lineages. SEs are clusters of regulatory elements enriched with transcriptional regulators, forming complex gene regulatory networks via differential binding patterns and the synchronized stimulation of multiple target genes. Although the exact role of SEs remains unclear, they are commonly found near master regulator genes for specific cell types and are implicated in the transcriptional regulation of tissue-specific stem cells and lineage determination. Additionally, super-enhancers play a crucial role in regulating cellular growth and differentiation in both normal development and disease pathologies. This review summarizes recent advances on SEs' role in placental development and the pathophysiology of placental diseases, emphasizing the potential for identifying SE-driven networks in the placenta to provide valuable insights for developing therapeutic strategies to address placental dysfunctions.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 2","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ting-Xin Jiang, Ping Wu, Ang Li, Randall B Widelitz, Cheng-Ming Chuong
{"title":"Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem Cells.","authors":"Ting-Xin Jiang, Ping Wu, Ang Li, Randall B Widelitz, Cheng-Ming Chuong","doi":"10.3390/jdb13020010","DOIUrl":"https://doi.org/10.3390/jdb13020010","url":null,"abstract":"<p><p>How to elicit and harness regeneration is a major issue in wound healing. Skin injury in most amniotes leads to repair rather than regeneration, except in hair and feathers. Feather follicles are unique organs that undergo physiological cyclic renewal, supported by a dynamic stem cell niche. During normal feather cycling, growth-phase proximal follicle collar bulge stem cells adopt a ring configuration. At the resting and initiation phases, these stem cells descend to the dermal papilla to form papillary ectoderm and ascend to the proximal follicle in a new growth phase. Plucking resting-phase feathers accelerates papillary ectoderm cell activation. Plucking growth-phase feathers depletes collar bulge stem cells; however, a blastema reforms the collar bulge stem cells, expressing KRT15, LGR6, Sox9, integrin-α6, and tenascin C. Removing the follicle base and dermal papilla prevents feather regeneration. Yet, transplanting an exogenous dermal papilla to the follicle base can induce re-epithelialization from the lower follicle sheath, followed by feather regeneration. Thus, there is a stepwise regenerative strategy using stem cells located in the collar bulge, papillary ectoderm, and de-differentiated lower follicle sheath to generate new feathers after different levels of injuries. This adaptable regenerative mechanism is based on the hierarchy of stem cell regenerative capacity and underscores the remarkable resilience of feather follicle regenerative abilities.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 2","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Varanid Teeth Asymmetry and Correlation to Body Size.","authors":"Guy Sion, Domenic C D'Amore","doi":"10.3390/jdb13010009","DOIUrl":"10.3390/jdb13010009","url":null,"abstract":"<p><p>Stressors such as injuries, embryonic instability during development, and higher levels of stress hormones such as testosterone can result in increases in fluctuating asymmetry in reptiles and other vertebrates. Digit asymmetry, digit ratio variability, and skull trait asymmetry such as eye and jaw size have been correlated with stress level in both snakes and lizards. Teeth asymmetry has also been used as a biomarker for stress and brain laterality. Body size is correlated with many potential stressors, yet there has been little research on how body size in reptiles relates to asymmetry. We investigate teeth asymmetry within the lizard family Varanidae, a clade with a diverse range of sizes consisting of the largest living lizard, <i>Varanus komodoensis</i>. Using a landmark/semi-landmark analysis, we derived Centroid Size for 671 pairs of teeth from 13 varanid species, and asymmetry was derived for each pair. Right-biased asymmetry was significantly greater in the upper tooth row, but breaking up tooth positions into further sections did not yield a significant difference. We found a significant positive linear correlation between body size and right-biased teeth directional asymmetry within <i>Varanus</i>, but only when excluding <i>V. komodoensis</i>. This significant correlation may result from fewer potential predators and more potential food items, thus resulting in less overall stress. When analyzed separately, <i>V. komodoensis</i> individuals with <180 mm head length demonstrated a positive, yet non-significant, trend along a similar trajectory to their congenerics with a high goodness of fit. On the other hand, individuals > 180 mm showed a high degree of scatter, with several specimens having pronounced left-biased asymmetry. We suspect that this dramatic change was due to a combination of ontogenetic niche shift, bigger home ranges, a greater susceptibility to negative anthropogenic influences, and/or a male bias in the bigger specimens sampled, but a larger sample size is required to determine if there is statistical significance in these intra-specific trends. Body asymmetry can reflect brain laterality, which may be a potential driver for the teeth asymmetry seen here.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vladimira Foteva, Joshua J Fisher, Yixue Qiao, Roger Smith
{"title":"Effects of Molybdenum Supplementation in the Form of Ammonium and Sodium Salts on Trophoblast Cell Physiology and Gene Expression In Vitro.","authors":"Vladimira Foteva, Joshua J Fisher, Yixue Qiao, Roger Smith","doi":"10.3390/jdb13010008","DOIUrl":"10.3390/jdb13010008","url":null,"abstract":"<p><p>Molybdenum is an essential trace element sourced during pregnancy from the maternal diet. Studies regarding molybdenum have primarily focused on overexposure in animal and cell culture studies. The effects of molybdenum supplementation on placental function are unknown. An immortalised trophoblast cell line was used to examine the placental cellular response to molybdenum in its bioavailable form as molybdate. Cells of the extravillous trophoblast first-trimester cell line HTR8-SVneo were cultured in complete cell media in the presence of 10 nM to 1 mM of ammonium molybdate or sodium molybdate. Following the addition of the molybdate salts, cell growth, viability, and several gene pathways were monitored. Sodium molybdate salt in doses from 10 nM to 1 mM did not affect cell growth or viability. Exposure to ammonium molybdate at a 1 mM concentration significantly decreased cell growth and viability (<i>p</i> < 0.05). Gene pathways involving molybdoenzyme expression, molybdenum cofactor synthesis, antioxidant response, and angiogenesis were affected following supplementation, although these effects differed depending on the dose and molybdate salt utilised. Molybdoenzyme activity was not affected by supplementation in a dose-dependent manner. The results indicate sodium molybdate is a more appropriate salt to use in vitro, as ammonium molybdate exposure reduced cell viability and growth and downregulated the expression of antioxidant genes <i>NFE2L2</i> (<i>p</i> < 0.01), <i>SOD1</i> (<i>p</i> < 0.001) and <i>SOD2</i> (<i>p</i> < 0.001), suggestive of an inflammatory response. Sodium molybdate affected gene, protein, and activity levels of molybdoenzyme, antioxidant, and angiogenic molecules in vitro. This work demonstrates that sodium molybdate supplementation has pleiotropic effects in vitro and is well tolerated by placental cells at a range of nanomolar and micromolar concentrations.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daisy Jihyung Ko, Tess Kelly, Lacey Thompson, Jasmene K Uppal, Nasim Rostampour, Mark Adam Webb, Ning Zhu, George Belev, Prosanta Mondal, David M L Cooper, Julia C Boughner
{"title":"Correction: Ko et al. Timing of Mouse Molar Formation Is Independent of Jaw Length Including Retromolar Space. <i>J. Dev. Biol.</i> 2021, <i>9</i>, 8.","authors":"Daisy Jihyung Ko, Tess Kelly, Lacey Thompson, Jasmene K Uppal, Nasim Rostampour, Mark Adam Webb, Ning Zhu, George Belev, Prosanta Mondal, David M L Cooper, Julia C Boughner","doi":"10.3390/jdb13010007","DOIUrl":"10.3390/jdb13010007","url":null,"abstract":"<p><p>There was an error in the original publication [...].</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaromír Vašíček, Andrej Baláži, Mária Tirpáková, Marián Tomka, Peter Chrenek
{"title":"Changes in the Intracellular Composition of Macro and Microminerals After Cryopreservation of the Rabbit Stem/Progenitor Cells.","authors":"Jaromír Vašíček, Andrej Baláži, Mária Tirpáková, Marián Tomka, Peter Chrenek","doi":"10.3390/jdb13010006","DOIUrl":"10.3390/jdb13010006","url":null,"abstract":"<p><p>Cryopreservation is a widely used method for the long-term preservation of reproductive or somatic cells. It is known that this storage method may negatively affect cell viability, proliferation, differentiation, etc. However, there is a lack of information about whether cryostorage can alter the content of intracellular minerals. Therefore, we focused this study on the analysis of the mineral composition of living cells before and after long-term cold storage. Briefly, three different primary cell lines were established from rabbits as follows: endothelial progenitor cells from peripheral blood (EPCs), endothelial progenitor cells from bone marrow (BEPCs), and mesenchymal stem cells from adipose tissue (AT-MSCs), which were cultured until passage 3 prior to cryopreservation in liquid nitrogen. Samples from freshly cultured and frozen-thawed cells were mineralized and analyzed using inductively coupled plasma-optical emission spectroscopy (ICP-OES) for the content of minerals (macro: Ca, Na, K, and Mg, and micro: Zn, Fe, Cu, Al, Co, Mn, Sr, and Ni). After cryopreservation, we found significantly decreased content of K in frozen-thawed EPCs (<i>p</i> < 0.01) and BEPCs (<i>p</i> < 0.0001) and Ca in AT-MSCs (<i>p</i> < 0.05), while Na was increased in frozen-thawed BEPCs (<i>p</i> < 0.05). Concentrations of Fe and Al were reduced significantly in frozen-thawed EPCs (both <i>p</i> < 0.0001) and AT-MSCs (<i>p</i> < 0.001 and <i>p</i> < 0.0001, respectively). On the contrary, Fe and Al were elevated in frozen-thawed BEPCs (<i>p</i> < 0.0001 and <i>p</i> < 0.01, respectively) together with Ni (<i>p</i> < 0.0001). In addition, decreased Zn (<i>p</i> < 0.05) was observed in cryopreserved AT-MSCs. In conclusion, the ICP-OES technique might be used to analyze the basic elemental composition of animal cells in fresh or frozen-thawed conditions. Nevertheless, additional studies are needed to reveal the possible impact of cryopreservation on cell fate by changing the content of intracellular minerals.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohamed I Elashry, Victoria C Schneider, Manuela Heimann, Sabine Wenisch, Stefan Arnhold
{"title":"CRISPR/Cas9-Targeted <i>Myostatin</i> Deletion Improves the Myogenic Differentiation Parameters for Muscle-Derived Stem Cells in Mice.","authors":"Mohamed I Elashry, Victoria C Schneider, Manuela Heimann, Sabine Wenisch, Stefan Arnhold","doi":"10.3390/jdb13010005","DOIUrl":"10.3390/jdb13010005","url":null,"abstract":"<p><p>Skeletal muscle plays a pivotal role in physical activity, protein storage and energy utilization. Skeletal muscle wasting due to immobilization, aging, muscular dystrophy and cancer cachexia has negative impacts on the quality of life. The deletion of myostatin, a growth and differentiation factor-8 (GDF-8) augments muscle mass through hyperplasia and hypertrophy of muscle fibers. The present study examines the impact of myostatin deletion using CRISPR/Cas9 editing on the myogenic differentiation (MD) of C2C12 muscle stem cells. A total of five myostatin loci were targeted using guided RNAs that had been previously cloned into a vector. The clones were transfected in C2C12 cells via electroporation. The cell viability and MD of myostatin-edited clones (Mstn<sup>-/-</sup>) were compared with C2C12 (Mstn<sup>+/+</sup>) using a series of assays, including MTT, sulforhodamine B, immunocytochemistry, morphometric analysis and RT-qPCR. The clones sequenced showed evidence of nucleotides deletion in Mstn<sup>-/-</sup> cells. Mstn<sup>-/-</sup> cells demonstrated a normal physiological performance and lack of cytotoxicity. Myostatin depletion promoted the myogenic commitment as evidenced by upregulated MyoD and myogenin expression. The number of MyoD-positive cells was increased in the differentiated Mstn<sup>-/-</sup> clones. The Mstn<sup>-/-</sup> editing upregulates both mTOR and MyH expression, as well as increasing the size of myotubes. The differentiation of Mstn<sup>-/-</sup> cells upregulates ActRIIb; in contrast, it downregulates decorin expression. The data provide evidence of successful CRISPR/Cas9-mediated myostatin deletion. In addition, targeting myostatin could be a beneficial therapeutic strategy to promote MD and to restore muscle loss. In conclusion, the data suggest that myostatin editing using CRISPR/Cas9 could be a potential therapeutic manipulation to improve the regenerative capacity of muscle stem cells before in vivo application.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sofia M Perez, Helena S Augustineli, Matthew R Marcello
{"title":"Utilizing <i>C. elegans</i> Spermatogenesis and Fertilization Mutants as a Model for Human Disease.","authors":"Sofia M Perez, Helena S Augustineli, Matthew R Marcello","doi":"10.3390/jdb13010004","DOIUrl":"10.3390/jdb13010004","url":null,"abstract":"<p><p>The nematode <i>C. elegans</i> is a proven model for identifying genes involved in human disease, and the study of <i>C. elegans</i> reproduction, specifically spermatogenesis and fertilization, has led to significant contributions to our understanding of cellular function. Approximately 70 genes have been identified in <i>C. elegans</i> that control spermatogenesis and fertilization (<i>spe</i> and <i>fer</i> mutants). This review focuses on eight genes that have human orthologs with known pathogenic phenotypes. Using <i>C. elegans</i> to study these genes has led to critical developments in our understanding of protein domain function and human disease, including understanding the role of <i>OTOF</i> (the ortholog of <i>C. elegans fer-1</i>) in hearing loss, the contribution of the <i>spe-39</i> ortholog <i>VIPAS39</i> in vacuolar protein sorting, and the overlapping functions of <i>spe-26</i> and <i>KLHL10</i> in spermatogenesis. We discuss the cellular function of both the <i>C. elegans</i> genes and their human orthologs and the impact that <i>C. elegans</i> mutants and human variants have on cellular function and physiology. Utilizing <i>C. elegans</i> to understand the function of the genes reviewed here, and additional understudied and undiscovered genes, represents a unique opportunity to understand the function of variants that could lead to better disease diagnosis and clinical decision making.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}