Lin Liu , Tomoki Chiba , Takahide Matsushima , Maiko Inotsume , Tomomi Kato , Yuichi Hiraoka , Hiroshi Asahara
{"title":"Gene dosage-dependent roles of Mkx in postnatal tendon development and maintenance revealed by conditional deletion","authors":"Lin Liu , Tomoki Chiba , Takahide Matsushima , Maiko Inotsume , Tomomi Kato , Yuichi Hiraoka , Hiroshi Asahara","doi":"10.1016/j.ydbio.2025.06.022","DOIUrl":"10.1016/j.ydbio.2025.06.022","url":null,"abstract":"<div><div>The transcription factor <em>Mohawk (Mkx)</em> contributes to tendon development and differentiation, as demonstrated by conventional knockout studies. However, the temporal requirements and gene dosage effects of <em>Mkx</em> in postnatal tendon maturation and maintenance remain unclear. To address these questions, we generated a novel conditional knockout mouse model harboring a loxP-flanked allele and a Venus-CreERT2 knock-in allele at the <em>Mkx</em> locus by crossing <em>Mkx</em> <sup><em>Venus-CreERT2/+</em></sup> with <em>Mkx</em> <sup><em>flox/+</em></sup> lines. Tamoxifen was administered at two distinct stages: early postnatal (P3) and adult (6-week-old). <em>Mkx</em> <sup><em>Venus-CreERT2/+</em></sup> mice exhibited mild reductions in tendon thickness and alterations in collagen fibril organization, while conditional deletion of <em>Mkx</em> (<em>Mkx</em> <sup><em>Venus-CreERT2/flox</em></sup> with tamoxifen induction) resulted in more pronounced defects. Time-course analysis revealed that both early postnatal and adult <em>Mkx</em> deletion led to progressive changes in tendon morphology, with TEM analysis showing a tendency toward reduced collagen fibril diameters. RNA-seq revealed distinct transcriptional changes associated with ECM organization and tendon homeostasis in <em>Mkx</em>-deficient tendons. These findings reveal previously unrecognized gene dosage effects of <em>Mkx</em> and suggest that maintaining appropriate levels of <em>Mkx</em> may be critical for tendon homeostasis, providing new insights into tendon biology and potential therapeutic strategies for tendon-related pathologies.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"526 ","pages":"Pages 15-25"},"PeriodicalIF":2.5,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Together forever: patterns and strategies of vertical symbiont transmission in planthoppers","authors":"Anna Michalik, Teresa Szklarzewicz","doi":"10.1016/j.ydbio.2025.06.020","DOIUrl":"10.1016/j.ydbio.2025.06.020","url":null,"abstract":"<div><div>Insects host a wide variety of microbial symbionts, including bacteria and fungi, which contribute to their survival by supplementing essential nutrients and aiding in adaptation to diverse ecological niches. The mode of symbiont transmission between generations, particularly vertical transmission, plays a central role in maintaining these mutualistic relationships. In this review, we focus on the transmission mechanisms of symbionts in planthoppers (Fulgoromorpha), a group of sap-feeding insects that rely heavily on obligate, nutritional symbionts for amino acid biosynthesis. These symbionts are transmitted through the ovary, with ancestral and newly acquired symbionts utilizing distinct strategies for vertical transmission. Here, we describe the conservative transmission mode for the ancient <em>Sulcia</em> and <em>Vidania</em> symbionts and show how more recent associates, including <em>Sodalis</em> and <em>Acetobacteraceae</em>, may adopt varied transmission routes. Moreover, we discuss the transmission strategies of facultative symbionts like <em>Wolbachia</em> and <em>Rickettsia</em>, illustrating the diversity of transmission pathways across different insect species. Lastly, we discuss the evolutionary consequences of long-term, strictly vertical symbiont transmission. This review synthesizes current knowledge on symbiont inheritance in planthoppers and identifies key areas for future research on insect-microbe symbioses.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"525 ","pages":"Pages 319-330"},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Calreticulin is required for cuticle deposition and trabeculae formation inside butterfly wing scale cells","authors":"Ru Hong, Cédric Finet, Antónia Monteiro","doi":"10.1016/j.ydbio.2025.06.013","DOIUrl":"10.1016/j.ydbio.2025.06.013","url":null,"abstract":"<div><div>Insect cuticle is normally deposited outside the plasma membrane of epidermal cells, making it unclear how cuticular pillars (trabeculae) are found inside butterfly wing scale cells. By co-labelling the cuticle and the plasma membrane, we found evidence that the plasma membrane invaginates towards the interior of the scale during development, and that chitin pillars form within these invaginations within the cell, but topologically outside it. Furthermore, we found that Calreticulin, a multifunctional protein, is essential for the formation of these trabeculae. The signal from an antibody targeting this protein was found colocalized with chitin outside the cell membrane, as scales were developing, and a <em>calreticulin</em> gene knockout led to loss of chitin pillars, disruption of other scale morphologies, and loss of pigmentation. Our results implicate this multifunctional protein in butterfly wing scale coloration and morphology.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"526 ","pages":"Pages 1-14"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victoria A. Deveau , Jessica A. Willson , Jennifer L. Carleton , Thomas A. Drysdale
{"title":"Differential requirement of Hand1 during differentiation of lateral plate mesoderm lineages in Xenopus laevis","authors":"Victoria A. Deveau , Jessica A. Willson , Jennifer L. Carleton , Thomas A. Drysdale","doi":"10.1016/j.ydbio.2025.06.005","DOIUrl":"10.1016/j.ydbio.2025.06.005","url":null,"abstract":"<div><div>The transcription factor <em>hand1</em> is expressed in the heart, lateral plate mesoderm (LPM) and neural crest cells during development. <em>Hand1</em>-null mice die early in embryogenesis due to defects in the heart and placenta. This lethality has made our understanding of the range of functions for Hand1 in early development incomplete. In <em>Xenopus</em>, we observed that the <em>hand1</em> expression pattern initially marked essentially all LPM derivatives and then correlated closely with a subset of specific LPM derivatives later in development. This led us to hypothesize that tight regulation of <em>hand1</em> is required for normal development of LPM lineages. Using <em>hand1</em> knockdown and overexpression models in <em>Xenopus</em>, development of LPM derivatives was compared. As in the mouse, we found that <em>hand1</em> is required for proper heart morphogenesis. <em>Hand1</em> is also required for the formation of a complex vascular plexus within embryos by maintaining early endothelial cell populations, however, <em>hand1</em> over expression is not sufficient to induce endothelial cell differentiation. Furthermore, down regulation of <em>hand1</em> is critical for the development of the hematopoietic lineages. These findings confirm a conserved role of <em>hand1</em> in heart morphogenesis and suggest regulation of <em>hand1</em> levels is critical for normal development of specific LPM lineages.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"525 ","pages":"Pages 294-305"},"PeriodicalIF":2.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shannon A. Weldon , Emily L. Smith , Magdalena Schatka , Leighton Folkes , Gi Fay Mok , Ashleigh Lister , Iain C. Macaulay , Wilfried Hearty , Andrea E. Münsterberg
{"title":"Transcriptomics and chromatin accessibility signatures define the cervical-thoracic boundary along the vertebrate axis","authors":"Shannon A. Weldon , Emily L. Smith , Magdalena Schatka , Leighton Folkes , Gi Fay Mok , Ashleigh Lister , Iain C. Macaulay , Wilfried Hearty , Andrea E. Münsterberg","doi":"10.1016/j.ydbio.2025.06.012","DOIUrl":"10.1016/j.ydbio.2025.06.012","url":null,"abstract":"<div><div>In vertebrate embryos, somite pairs form on either side of the neural tube along the main body axis. Somites generate the tissues of the musculoskeletal system, including cartilage of the vertebral column and ribs and skeletal muscles of the trunk and limbs. The detailed anatomy of somite-derived tissues varies along the axis, with unique features most easily visible in the vertebral column. Here we investigate the genetic control of this regionalization, which drives the subsequent cell differentiation programmes, focusing on the cervical to thoracic (C-T) boundary. Using ATAC-sequencing and RNA-sequencing, we establish molecular profiles of somites, in particular the chromatin landscapes and transcriptional programmes, that define this anatomical transition. Differential analysis highlights candidate <em>cis</em>-regulatory elements (CRE), and <em>in silico</em> footprints identify coverage of transcription factor (TF) binding sites associated with differentially expressed genes. Electroporation of citrine reporters <em>in vivo</em> validates the activity of CREs associated with key HOX genes, HOXC6 and HOXC8. HOXC6 footprints indicate its role in regulating a trio of differentially expressed SOX transcription factors, SOX5, SOX6 and SOX9, which are involved in chondrogenesis. In addition, the differential analysis identifies several lncRNAs, including one that is located within the HOXC cluster. CRISPR-on experiments suggest HOXC6 regulates its expression and therefore we name it lncRNA-HOXC6TA, however, its function in the thoracic region is currently unknown. Our study provides valuable datasets and illustrates how they can be mined to gain further insights into the regulatory mechanisms underlying the C-T transition along the vertebrate body axis.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"525 ","pages":"Pages 249-258"},"PeriodicalIF":2.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reintegration of blastema and stump by reciprocal interaction for functional joint regeneration in frogs","authors":"Haruka Matsubara , Takeshi Inoue , Kiyokazu Agata","doi":"10.1016/j.ydbio.2025.06.011","DOIUrl":"10.1016/j.ydbio.2025.06.011","url":null,"abstract":"<div><div>Previous studies suggested the importance of the reciprocal interactions between residual tissues, which we refer to here as the “stump”, and the newly formed tissues, referred to as the “blastema”, for achieving functional joint regeneration after amputation at the elbow joint level in newts. This reciprocal interaction during regeneration was named “reintegration”. When this reintegration mechanism was evoked in the frog <em>Xenopus leavis</em>, regeneration of a functional elbow joint was induced. Interestingly, degradation of extracellular matrix (ECM) in the remaining joint articular cartilage was observed during regeneration in both newts and frogs. Histological and gene expression analyses suggested that the degradation of Type II collagen in the cartilage of the articular head might be performed by matrix metalloproteases (Mmps) that were transiently expressed after amputation. Here we found that fibroblast growth factor (Fgf) induced Mmps expression in the cartilage of the articular head. These results support the possibility that the Fgf signal induces ECM degradation in joint tissues via Mmps expression and that the ECM degradation and subsequent bone morphogenetic protein (Bmp) secretion promote cell proliferation, migration, and differentiation of the cells in the blastema to achieve functional joint regeneration.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"525 ","pages":"Pages 282-293"},"PeriodicalIF":2.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Wang , Yangyi Xu , Zhaoyang Guo, Nusrat Hasan Kanika, Xin Hou, Xiaowen Chen, Chenghui Wang
{"title":"Regenerative growth in Eriocheir sinensis is driven by Slc7a5-TORC1-regulated cell signaling","authors":"Jun Wang , Yangyi Xu , Zhaoyang Guo, Nusrat Hasan Kanika, Xin Hou, Xiaowen Chen, Chenghui Wang","doi":"10.1016/j.ydbio.2025.06.010","DOIUrl":"10.1016/j.ydbio.2025.06.010","url":null,"abstract":"<div><div>Limb regeneration is a widespread phenomenon among animals, yet the underlying molecular mechanisms remain incompletely understood. Crustaceans like the Chinese mitten crab (<em>Eriocheir sinensis</em>), possess the remarkable ability to regrow lost limbs through a highly regulated regenerative process. In this study, we investigated the molecular mechanisms underlying limb regeneration in <em>E</em>. <em>sinensis</em> by integrating morphological and histological analyses, spatiotemporal mRNA expression profiling of TORC1 pathway genes, and RNA interference of <em>Slc7a5</em> and <em>TOR</em> genes. Our results demonstrated that key genes within the TORC1 pathway, including <em>Vatb</em>, <em>Rraga</em>, <em>Rragd</em>, <em>TOR</em>, and <em>S6K1</em>, exhibit distinct expression patterns at different stages of limb regeneration, varying across developmental periods. Furthermore, in-situ hybridization and targeted knockdown of <em>Slc7a5</em> and <em>TOR</em> genes significantly affected the rate of limb regeneration, highlighting their crucial roles in promoting blastema formation, papilla development, and ultimately, limb regeneration. Overall, our research reveals that <em>Slc7a5</em> gene regulation within the TORC1 pathway significantly influences cell proliferation during limb regeneration in <em>E. sinensis</em>, thereby advancing our understanding of the role of TORC1 signaling in crustacean limb regeneration.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"525 ","pages":"Pages 240-248"},"PeriodicalIF":2.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Katherine Johnson , Larisa L. Litovchick , Amanda J.G. Dickinson
{"title":"The role of Goldilocks protein kinase DYRK1A in embryonic development","authors":"H. Katherine Johnson , Larisa L. Litovchick , Amanda J.G. Dickinson","doi":"10.1016/j.ydbio.2025.06.009","DOIUrl":"10.1016/j.ydbio.2025.06.009","url":null,"abstract":"<div><div>DYRK1A (Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) is a dosage-sensitive gene whose expression must be tightly regulated to support normal development. This is supported by studies in animal models which demonstrate that both insufficient and excessive DYRK1A/Dyrk1a activity can impair development across multiple organ systems. In humans, both gain and loss-of-function alterations can disrupt the levels of DYRK1A, leading to structural birth defects and neurodevelopmental disorders. For example, <em>DYRK1A</em> haploinsufficiency causes <em>DYRK1A</em> syndrome, marked by intellectual disability and characteristic craniofacial features. <em>DYRK1A</em> is located on chromosome 21, and its overexpression in the context of trisomy 21 is believed to contribute to the developmental anomalies and comorbidities seen in Down syndrome. Notably, normalizing DYRK1A genetically or pharmacologically in Down syndrome mouse models can partially rescue phenotypes, underscoring its pathogenic role in this genetic condition. This review highlights the critical need to understand the effects of altering <em>DYRK1A</em> dosage during embryogenesis to inform therapeutic strategies for <em>DYRK1A</em> related disorders and Down syndrome associated birth defects.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"525 ","pages":"Pages 216-228"},"PeriodicalIF":2.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"lmod2a mutations affect F-actin and SRF pathway leading to cardiac dysfunction in zebrafish","authors":"Xuebin Ye , Haiwang Jia , Yao Zu","doi":"10.1016/j.ydbio.2025.06.002","DOIUrl":"10.1016/j.ydbio.2025.06.002","url":null,"abstract":"<div><div>Leiomodin 2 (LMOD2), a critical pathogenic gene associated with human dilated cardiomyopathy (DCM), is essential in regulating thin filament length during cardiac development. This study generated a homozygous knockout zebrafish line (<em>lmod2a</em><sup><em>−/−</em></sup>) using CRISPR/Cas9 genome editing. <em>lmod2a</em><sup><em>−/−</em></sup> embryos exhibited impaired locomotor activity alongside irregular heart rhythms, reduced cardiac output, compromised contractility, and delayed calcium transients, as revealed by high-speed imaging and calcium optical mapping. Immunofluorescence staining demonstrated a marked reduction in filamentous actin (F-actin), corroborated by QPCR data showing downregulation of the F-actin marker gene <em>acta1b</em>. Moreover, expression levels of key downstream targets of the serum response factor (SRF) signaling pathway were markedly reduced in mutants. These findings indicate that <em>lmod2a</em> deficiency disrupts F-actin homeostasis and SRF-mediated gene regulation, ultimately leading to defective cardiac performance. This study establishes a novel zebrafish model for investigating <em>LMOD</em>-associated cardiomyopathies and provides valuable insights for future therapeutic interventions targeting actin-related cardiac disorders.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"525 ","pages":"Pages 306-316"},"PeriodicalIF":2.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}