{"title":"The Intersex Gene Is Crucial for Female Fertility and Embryonic Viability in the Red Flour Beetle, Tribolium castaneum","authors":"Chhavi Choudhary, Siddhi Paliwal, Keshav Kumar Meghwanshi, Sundaram Shilpi, Jayendra Nath Shukla","doi":"10.1002/dvg.70051","DOIUrl":"https://doi.org/10.1002/dvg.70051","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>intersex</i> (<i>ix</i>) plays a pivotal role in the sex determination pathway of Drosophila melanogaster. The <i>Drosophila</i> Ix protein interacts with female-specific Doublesex protein to regulate female sexual differentiation. In this study, we functionally characterized the <i>ix</i> homologue (<i>Tcix</i>) in the red flour beetle, <i>Tribolium castaneum</i>. The <i>Tcix</i> gene comprises of four exons and three introns, and encodes a protein of 166 amino acids that contains a conserved ‘Mediator complex subunit 29’ (Med-29) domain. The pre-mRNA of <i>Tcix</i> splices in a non-sex-specific manner and is expressed across all the developmental stages of <i>T. castaneum</i>. RNA interference-mediated knockdown of <i>Tcix</i> in adult beetles led to a significant reduction in its expression in both sexes. Knockdown males did not show any phenotypic changes, but knockdown females displayed compromised ovarian development, resulting in reduced fecundity and failure of eggs to hatch. Interestingly, the expression of <i>vitellogenin-1</i> (<i>Vg-1</i>), a key gene involved in oocyte development, was significantly downregulated in these females. Further, parental RNAi of <i>Tcix</i> demonstrated the failure in the hatching of eggs, despite no significant effects on the number of eggs laid. The phylogenetic analysis of <i>Tcix</i> revealed its close clustering with other coleopterans, which supports its evolutionary conservation. Overall, our study establishes the critical role of <i>Tcix</i> in female fertility and embryonic development in <i>T. castaneum</i>.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Intersex Gene Is Crucial for Female Fertility and Embryonic Viability in the Red Flour Beetle, Tribolium castaneum","authors":"Chhavi Choudhary, Siddhi Paliwal, Keshav Kumar Meghwanshi, Sundaram Shilpi, Jayendra Nath Shukla","doi":"10.1002/dvg.70051","DOIUrl":"https://doi.org/10.1002/dvg.70051","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>intersex</i> (<i>ix</i>) plays a pivotal role in the sex determination pathway of Drosophila melanogaster. The <i>Drosophila</i> Ix protein interacts with female-specific Doublesex protein to regulate female sexual differentiation. In this study, we functionally characterized the <i>ix</i> homologue (<i>Tcix</i>) in the red flour beetle, <i>Tribolium castaneum</i>. The <i>Tcix</i> gene comprises of four exons and three introns, and encodes a protein of 166 amino acids that contains a conserved ‘Mediator complex subunit 29’ (Med-29) domain. The pre-mRNA of <i>Tcix</i> splices in a non-sex-specific manner and is expressed across all the developmental stages of <i>T. castaneum</i>. RNA interference-mediated knockdown of <i>Tcix</i> in adult beetles led to a significant reduction in its expression in both sexes. Knockdown males did not show any phenotypic changes, but knockdown females displayed compromised ovarian development, resulting in reduced fecundity and failure of eggs to hatch. Interestingly, the expression of <i>vitellogenin-1</i> (<i>Vg-1</i>), a key gene involved in oocyte development, was significantly downregulated in these females. Further, parental RNAi of <i>Tcix</i> demonstrated the failure in the hatching of eggs, despite no significant effects on the number of eggs laid. The phylogenetic analysis of <i>Tcix</i> revealed its close clustering with other coleopterans, which supports its evolutionary conservation. Overall, our study establishes the critical role of <i>Tcix</i> in female fertility and embryonic development in <i>T. castaneum</i>.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
genesisPub Date : 2026-04-13DOI: 10.1002/dvg.70052
H. Herrera-Orozco, H. A. Pérez-Mendoza
{"title":"Metamorphosis and lncRNAs: A Close Relationship","authors":"H. Herrera-Orozco, H. A. Pérez-Mendoza","doi":"10.1002/dvg.70052","DOIUrl":"https://doi.org/10.1002/dvg.70052","url":null,"abstract":"<p>The classical definition of metamorphosis is a post-embryonic transformation, such as from a tadpole to a froglet. However, recent studies suggest this process occurs to some degree in all vertebrates, as the underlying endocrine and molecular pathways are highly conserved. With the advent of high-throughput sequencing, transcriptomic data for non-model species has revealed that protein-coding genes represent only a small fraction of the genome. In contrast, most transcriptional output produces non-coding RNAs with vital regulatory functions. Among these, long non-coding RNAs are a diverse and important class known to regulate gene expression at multiple levels and across various biological contexts. Despite their established importance, the study of lncRNAs across the tree of life remains an open field, crucial for understanding their potential roles and evolutionary conservation. This work summarizes the roles of lncRNAs as regulatory molecules, their functions in development and metamorphosis, computational strategies for their characterization, and the challenges and opportunities of studying them in non-model species.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
genesisPub Date : 2026-04-13DOI: 10.1002/dvg.70052
H. Herrera-Orozco, H. A. Pérez-Mendoza
{"title":"Metamorphosis and lncRNAs: A Close Relationship","authors":"H. Herrera-Orozco, H. A. Pérez-Mendoza","doi":"10.1002/dvg.70052","DOIUrl":"https://doi.org/10.1002/dvg.70052","url":null,"abstract":"<p>The classical definition of metamorphosis is a post-embryonic transformation, such as from a tadpole to a froglet. However, recent studies suggest this process occurs to some degree in all vertebrates, as the underlying endocrine and molecular pathways are highly conserved. With the advent of high-throughput sequencing, transcriptomic data for non-model species has revealed that protein-coding genes represent only a small fraction of the genome. In contrast, most transcriptional output produces non-coding RNAs with vital regulatory functions. Among these, long non-coding RNAs are a diverse and important class known to regulate gene expression at multiple levels and across various biological contexts. Despite their established importance, the study of lncRNAs across the tree of life remains an open field, crucial for understanding their potential roles and evolutionary conservation. This work summarizes the roles of lncRNAs as regulatory molecules, their functions in development and metamorphosis, computational strategies for their characterization, and the challenges and opportunities of studying them in non-model species.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
genesisPub Date : 2026-03-26DOI: 10.1002/dvg.70049
{"title":"Correction to “Roles of Osteoclasts in Alveolar Bone Remodeling”","authors":"","doi":"10.1002/dvg.70049","DOIUrl":"10.1002/dvg.70049","url":null,"abstract":"<p>\u0000 <span>Omi, M.</span>, and <span>Y. Mishina</span>. <span>2022</span>. “ <span>Roles of Osteoclasts in Alveolar Bone Remodeling</span>.” <i>Genesis</i> <span>60</span>, no. <span>8–9</span>: e23490. https://doi.org/10.1002/dvg.23490.\u0000 </p><p>Since the article's publication, a taxonomic inaccuracy has come to the attention of the authors. Instead of <i>Tannerella forsythensis</i>, the periodontal pathogen should be referred to by the correct name <i>Tannerella forsythia</i>.</p><p>We apologize for this error.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
genesisPub Date : 2026-03-16DOI: 10.1002/dvg.70047
Yong Yuan, Josiah Holt, Samuel Lorry, Yen-Chiao Wang, Yueh-Chiang Hu, Zhixing Ma, Adam Kaufman, Winston Kao, Diego G. Ogando, Chia-Yang Liu
{"title":"Generation of a Novel Col8a2P2A-CreERT2 Mouse Line Enables Targeted Genetic Manipulation of Corneal Endothelial Cells and Modeling of Endothelial Decompensation","authors":"Yong Yuan, Josiah Holt, Samuel Lorry, Yen-Chiao Wang, Yueh-Chiang Hu, Zhixing Ma, Adam Kaufman, Winston Kao, Diego G. Ogando, Chia-Yang Liu","doi":"10.1002/dvg.70047","DOIUrl":"10.1002/dvg.70047","url":null,"abstract":"<p>The corneal endothelium is a monolayer of specialized cells that maintains stromal deturgescence and transparency, functions essential for vision. Despite its clinical importance, the developmental origins and homeostatic programs of the endothelium remain poorly understood, in part due to the lack of a lineage-specific genetic driver. To overcome this limitation, we generated a <i>Col8a2</i><sup><i>P2A-CreERT2</i></sup> knock-in mouse line that enables selective genetic manipulations of corneal endothelial cells. Cre activity was validated with reporter alleles and functional importance was assessed by conditional ablation of Col8a2<sup>+</sup> cells in adulthood, with phenotypic outcomes evaluated by histology, immunofluorescence, and in vivo imaging. We found that <i>Col8a2</i><sup><i>P2A-CreERT2</i></sup> drives robust and specific recombination in corneal endothelial cells. Functional assays demonstrated that Col8a2<sup>+</sup> cells contribute continuously to Descemet's membrane synthesis and are essential for maintaining endothelial integrity. Ablation disrupted endothelial density and barrier function, resulting in phenotypes resembling human endothelial dystrophies, including features of Fuchs' endothelial corneal dystrophy and posterior polymorphous corneal dystrophy. These findings identify Col8a2<sup>+</sup> cells as indispensable regulators of endothelial development, homeostasis, and disease pathogenesis. The <i>Col8a2</i><sup><i>P2A-CreERT2</i></sup> line provides the first corneal endothelium–specific genetic driver, establishing a platform for mechanistic investigation and therapeutic discovery in endothelial disorders.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12993115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
genesisPub Date : 2026-03-16DOI: 10.1002/dvg.70046
Robert J. Danaher, Vanessa Alves Handel, Lei Wang, Octavio A. Gonzalez
{"title":"Male Keratin 13-Cre Expression Causes Unanticipated Germline Deletion in Notch1 Floxed Mice","authors":"Robert J. Danaher, Vanessa Alves Handel, Lei Wang, Octavio A. Gonzalez","doi":"10.1002/dvg.70046","DOIUrl":"10.1002/dvg.70046","url":null,"abstract":"<div>\u0000 \u0000 <p>Notch1 receptor activation plays an important role in epithelial homeostasis and immunoregulation; however, its role in oral mucosal immunity remains unknown. Testing the impact of epithelial Notch1 activation in oral innate responses, including antimicrobial proteins like phospholipase A<sub>2</sub> group IIA (PLA<sub>2</sub>-IIA), requires epithelial-specific <i>Notch1</i> knockout mice. Creating Balb/c; K13Cre; Notch1<sup>Flox/Flox</sup> mice was initiated by crossing C57BL/6; K13Cre; Notch1<sup>Flox/Flox</sup> mice (naturally deficient for PLA<sub>2</sub>-IIA), expressing Cre recombinase under the control of the Krt13 (keratin 13) promoter (K13Cre) and Notch1<sup>Flox/Flox</sup> alleles to PLA<sub>2</sub>-IIA expressing Balb/c mice to generate Balb/c:C57BL/6; K13Cre; Notch1<sup>Flox</sup> heterozygotes and to ultimately create Balb/c; K13Cre; Notch1<sup>Flox/Flox</sup> (<i>Notch1</i> deficient) and Balb/c; Notch1<sup>Flox/Flox</sup> WT littermate controls. While all first-generation non-K13Cre expressing mice had the expected Notch1<sup>Flox</sup> heterozygote Notch1 genotype, surprisingly, all first-generation K13Cre expressing mice had an apparent K13Cre; Notch1 homozygote genotype, which is impossible when crossing Notch1 and Notch1<sup>Flox/Flox</sup> homozygotes. We found that the absence of the floxed Notch1 PCR amplicon resulted from recombination between the two LoxP sites flanking the forward Notch1 PCR primer, and the recombined <i>Notch1</i> allele was present in the germline of first-generation congenic mice. Finally, we show that this unexpected recombination is avoided by using female K13Cre; Notch1<sup>Flox</sup> donors and is a cautionary reminder that individual promoters are expressed during spermiogenesis.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
genesisPub Date : 2026-03-16DOI: 10.1002/dvg.70045
Yiwen Ma, Xiaorui Li, Liping Xiao, Ying Wang, Wei Zheng, Guilian Liang, Tao Sun
{"title":"Role of BARX1 in Development and Disease","authors":"Yiwen Ma, Xiaorui Li, Liping Xiao, Ying Wang, Wei Zheng, Guilian Liang, Tao Sun","doi":"10.1002/dvg.70045","DOIUrl":"10.1002/dvg.70045","url":null,"abstract":"<div>\u0000 \u0000 <p>Homeobox genes encode diverse proteins, including proteins with highly conserved DNA-binding domains, and are essential for organismal growth, cell differentiation, organ development, and diverse physiological processes associated with diseases. <i>BARX1</i> encodes a transcription factor containing the BarH1-like homeodomain. This gene plays a significant role in the development of various tissues and is closely associated with the pathogenesis and progression of numerous diseases. In this review, we provide a comprehensive overview of the functional networks and mechanisms of action of the <i>BARX1</i> gene across different tissue developmental processes and disease contexts.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Gfrα3 Conditional Knockout Mouse Reveals a Requirement for GFRα3/RET Signaling in Cholecystokinin-Positive Enteroendocrine Cells","authors":"Susan Simanjaya, Masato Kinoshita, Mukhamad Sunardi, Keisuke Ito, Masakazu Shinohara, Takaya Abe, Yuzo Kodama, Toshihiro Uesaka, Hideki Enomoto","doi":"10.1002/dvg.70043","DOIUrl":"10.1002/dvg.70043","url":null,"abstract":"<div>\u0000 \u0000 <p>The receptor tyrosine kinase RET regulates the development of multiple neuronal populations through GFRα co-receptors and their cognate ligands. Recent work has shown that RET is also required for enteroendocrine cell (EEC) function; however, the specific GFRα receptor operating in EECs has remained unclear. Here, we identify GFRα3 as the predominant GFRα receptor expressed in EECs. To determine its cell-autonomous role, we generated a <i>Gfrα3</i> conditional allele and inactivated the <i>Gfrα3</i> gene specifically in the intestinal epithelium. These <i>Gfrα3</i> IEcKO mice exhibited a selective reduction in the number of CCK<sup>+</sup> EECs among multiple EEC subtypes. A comparative decrease in CCK<sup>+</sup> EECs in <i>Ret</i> IEcKO mice suggests that RET/GFRα3 signaling is required for the development and/or maintenance of this EEC lineage. Although CCK<sup>+</sup> EECs can indirectly influence glucose metabolism, <i>Gfrα3</i> IEcKO mice showed no significant change in glucose tolerance under high-fat diet (HFD) conditions. In contrast, they exhibited modest lipid malabsorption on HFD. Together, these findings demonstrate that GFRα3 is implicated in the structure and function of CCK EECs and highlight the utility of the <i>Gfrα3</i> conditional allele for dissecting the biology of GFRα3-expressing cells.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
genesisPub Date : 2026-02-13DOI: 10.1002/dvg.70032
Kin Ming Kwan, Paul Trevorrow
{"title":"Meet Our Editorial Board—Kin Ming Kwan, Chinese University of Hong Kong, Hong Kong, China","authors":"Kin Ming Kwan, Paul Trevorrow","doi":"10.1002/dvg.70032","DOIUrl":"10.1002/dvg.70032","url":null,"abstract":"","PeriodicalId":12718,"journal":{"name":"genesis","volume":"64 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}