Developmental Dynamics最新文献

{"title":"Whole tissue imaging of cellular boundaries at sub-micron resolutions for deep learning cell segmentation: Applications in the analysis of epithelial bending of ectoderm.","authors":"Sam C P Norris, Jimmy K Hu, Neil H Shubin","doi":"10.1002/dvdy.70061","DOIUrl":"https://doi.org/10.1002/dvdy.70061","url":null,"abstract":"<p><strong>Background: </strong>To understand cellular morphology, biologists have relied on traditional optical microscopy of tissues combined with tissue clearing protocols to image structures deep within tissues. Unfortunately, these protocols often struggle to retain cell boundary markers, especially at high enough resolutions necessary for precise cell segmentation. This limitation affects the ability to study changes in cell shape during major developmental events.</p><p><strong>Results: </strong>We introduce a method that preserves cell boundary markers and matches the refractive index of tissues with water. This technique enables the use of high-magnification, long working distance water-dipping objectives that provide sub-micron resolution images. We subsequently segment individual cells using a trained neural network segmentation model. These segmented images facilitate quantification of cell properties of the entire three-dimensional tissue. As a demonstration, we examine mandibles of transgenic mice that express fluorescent proteins in their cell membranes and extend this technique to a non-model animal, the catshark, investigating its dental lamina and dermal denticles-invaginating and evaginating ectodermal structures, respectively. This technique provides insight into the mechanical environment that cells experience during developmental transitions.</p><p><strong>Conclusions: </strong>This pipeline, named MORPHOVIEW, provides a powerful tool to quantify in high throughput the 3D structures of cells and tissues during organ morphogenesis.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728711","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":"Streptozotocin induced hyperglycemia in the axolotl.","authors":"Pernille Lajer Sørensen, Anita Dittrich, Henrik Lauridsen","doi":"10.1002/dvdy.70063","DOIUrl":"https://doi.org/10.1002/dvdy.70063","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is a group of diseases characterized by loss of β cell mass and/or function, resulting in hyperglycemia. With no established curative treatment, this has initiated research in β cell regeneration. Current animal models have either limited regenerative capacity (mice) or small size and evolutionary distance from humans (zebrafish). There is a need for new models to study endogenous regeneration pathways. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells and aims to establish a protocol for STZ-induced hyperglycemia to mimic a diabetic state.</p><p><strong>Results: </strong>In this pilot study, five streptozotocin (STZ) protocols were tested, and the most effective one was identified on the basis of glucose tolerance tests. Blood glucose levels were monitored to track both disease progression and remission. Histological examination of the pancreas and systemic effects of STZ treatment were also evaluated.</p><p><strong>Conclusion: </strong>Induction of a diabetes-like state (hyperglycemia) in axolotls was possible with STZ, but variability among animals suggests the need for a higher degree of normalization or larger sample sizes. Histological regeneration was not observed, though blood glucose levels normalized over time. Some STZ-treated animals developed edema, but its cause remains unknown.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689428","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":"Pancreatic injury induces β-cell regeneration in axolotl.","authors":"Connor J Powell, Hani D Singer, Ashley R Juarez, Ryan T Kim, Elane Kim, Duygu Payzin-Dogru, Aaron M Savage, Noah J Lopez, Kara Thornton, Steven J Blair, Adnan Abouelela, Anita Dittrich, Stuart G Akeson, Miten Jain, Jessica L Whited","doi":"10.1002/dvdy.70060","DOIUrl":"10.1002/dvdy.70060","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is a condition characterized by a loss of pancreatic β-cell function, which results in the dysregulation of insulin homeostasis. Using a partial pancreatectomy model in axolotl, we aimed to observe the pancreatic response to injury.</p><p><strong>Results: </strong>Here we show a comprehensive histological characterization of pancreatic islets in axolotl. Following pancreatic injury, no apparent blastema-like structure was observed. We found a significant, organ-wide increase in cellular proliferation post-resection in the pancreas compared to sham-operated controls. This proliferative response was most robust at the site of injury. Further, an increase in nuclear density was observed, suggesting compensatory congestion as a mechanism of regeneration. We found that β-cells actively contributed to the increased rates of proliferation upon injury. β-Cell proliferation manifested in increased β-cell mass in injured tissue at 2 weeks post-injury. At 4 weeks post-injury, we found organ-wide proliferation to be extinguished while proliferation at the injury site persisted, corresponding to pancreatic tissue recovery. Similarly, total β-cell mass was comparable to sham after 4 weeks.</p><p><strong>Conclusions: </strong>Our findings suggest a non-blastema-mediated regeneration process takes place in the pancreas, by which pancreatic resection induces whole-organ β-cell proliferation without the formation of a blastemal structure. This process is analogous to other models of compensatory congestion in axolotl.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658691","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":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.70057","DOIUrl":"https://doi.org/10.1002/dvdy.70057","url":null,"abstract":"&lt;p&gt;Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in &lt;i&gt;Developmental Dynamics&lt;/i&gt; that illustrate the complex dynamics of developmental biology.&lt;/p&gt;&lt;p&gt;“Neural induction: New insight into the default model and an extended four-step model in vertebrate embryos” by Mohsen Saghal, &lt;i&gt;DevDyn&lt;/i&gt; 254.7, pp. 785-811, https://doi.org/10.1002/dvdy.70002. Neural induction is the process by which naive or uncommitted ectodermal cells differentiate into neural progenitor cells and ultimately give rise to the central and peripheral nervous systems. In vertebrates, this is thought to involve the inhibition of BMP signaling, mediated by the underlying mesoderm. Neural differentiation was therefore considered the default fate of naïve ectoderm unless instructed to acquire an epidermal cell fate in the presence of BMP signaling. However, both FGF signaling activation and Wnt inhibition were subsequently found to be required to suppress the BMP signaling, leading to a “pro-FGF” model of neural induction. This review highlights historical and recent findings that elucidate the mechanism of neural induction in vertebrates, and the author proposes a more refined four-step Activation, Stabilization, Transformation, and Elongation model of neural induction.&lt;/p&gt;&lt;p&gt;“Urodele amphibian newt bridges the missing link in evo-devo of the pancreas” by Ryosuke Morozumi, Kazuko Okamoto, Eriko Enomoto, Yuta Tsukamoto, Mitsuki Kyakuno, Nanoka Suzuki, Ichiro Tazawa, Nobuaki Furuno, Hajime Ogino, Yasuhiro Kamei, Masatoshi Matsunami, Shuji Shigenobu, Kenichi Suzuki, Hitoshi Uemasu, Noriyuki Namba, and Toshinori Hayashi, &lt;i&gt;DevDyn&lt;/i&gt; 254.7, pp. 812-828. https://doi.org/10.1002/dvdy.763. The pancreas in mammals, performs an exocrine function by producing pancreatic juice containing various digestive enzymes, and an endocrine function, by producing several hormones that regulate blood glucose levels. The acquisition of an endocrine function occurred during the fish to amphibian transition, highlighting the evolutionary significance of amphibians in pancreas development. To date, most studies on amphibian pancreas development and physiology have centered on anurans, and most notably &lt;i&gt;Xenopus&lt;/i&gt;. By comparison, pancreas development and function in urodeles, such as newts, remains underexplored. This study investigated the development of the pancreas in the urodele, &lt;i&gt;Pleurodeles waltl&lt;/i&gt;, revealing that the pancreas in the newt comprises a single organ with exocrine tissue characterized by acinar structures and endocrine tissue forming islets. Furthermore, the newt possesses unique pancreas-like tissues on their intestines. Thus, the newt pancreas exhibits a morphology similar to that of the mamma","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 7","pages":"783-784"},"PeriodicalIF":2.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomy connected 2025: American Association for Anatomy's annual meeting scientific research abstracts","authors":"","doi":"10.1002/dvdy.70058","DOIUrl":"https://doi.org/10.1002/dvdy.70058","url":null,"abstract":"","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 7","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647359","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":"Identification of neural crest and melanoma cancer cell invasion and migration genes using high-throughput screening and deep attention networks.","authors":"J C Kasemeier-Kulesa, S Martina Perez, R E Baker, P M Kulesa","doi":"10.1002/dvdy.70059","DOIUrl":"10.1002/dvdy.70059","url":null,"abstract":"<p><strong>Background: </strong>Cell migration and invasion are well-coordinated in development and disease but remain poorly understood. We previously showed that the neural crest (NC) cell migratory wavefront shares a 45-gene panel with other cell invasion phenomena. To rapidly and systematically identify critical genes, we performed a high-throughput siRNA screen and statistical and deep learning analyses to determine changes in NC- versus non-NC-derived human cell line behaviors.</p><p><strong>Results: </strong>We find 14 out of 45 genes significantly reduced c8161 melanoma cell migration; four of the 14 genes altered leader cell motility (BMP4, ITGB1, KCNE3, and RASGRP1). Deep learning identified marked disruptions in cell-neighbor interactions after BMP4 or RASGRP1 knockdown in c8161 cells. Recombinant proteins added to the culture media revealed five out of the 11 known secreted molecules stimulated c8161 cell migration. BMP4 knockdown severely reduced c8161 in vivo invasion in a chick embryo transplant model. Addition of BMP4 protein to the culture media of BMP4-siRNA-treated c8161 cells rescued cell migratory ability.</p><p><strong>Conclusion: </strong>High-throughput screening and deep learning distilled a 45-gene panel to a small subset of genes critical to melanoma and warrant deeper in vivo functional analysis for their role and potential synergies in driving NC cell migration and invasion.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599659","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":"Robinow syndrome DVL1 variants disrupt morphogenesis and appendage formation in a Drosophila disease model.","authors":"Gamze Akarsu, Katja R MacCharles, Kenneth Kin Lam Wong, Joy M Richman, Esther M Verheyen","doi":"10.1002/dvdy.70056","DOIUrl":"https://doi.org/10.1002/dvdy.70056","url":null,"abstract":"<p><strong>Background: </strong>Robinow syndrome is a rare developmental syndrome caused by variants in genes in Wnt signaling pathways. We previously showed that expression of patient variants in Dishevelled 1 (DVL1) in Drosophila and chicken models disrupts the balance of canonical and non-canonical Wnt signaling.</p><p><strong>Results: </strong>In this study, we further examine morphological changes that occur due to expression of DVL1^1519ΔT, which serves as a prototype for other pathogenic variants. We show that epithelial imaginal disc development is disrupted in legs and wings and accompanied by increased cell death, without changes in cell proliferation. By inhibiting caspase-dependent cell death, we show that the altered epithelial morphology is not solely due to variant-induced cell death. Furthermore, we find alterations of basement membrane components and modulators. Notably we find ectopic Mmp1 expression and tissue distortion, which is dependent on JNK signaling. We also find an abnormal abundance of Drosophila collagen IV (Viking) in pupal wing development. Due to the complex nature of appendage development, we also examined the Bone Morphogenetic Protein pathway and found elevated signaling activity via the transcriptional readout dad-lacZ.</p><p><strong>Conclusions: </strong>Through these studies, we have gained more insight into the developmental consequences of DVL1 variants implicated in autosomal dominant Robinow syndrome.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539512","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":"Endoderm differentiates into a transient epidermis in the mouse perineum.","authors":"Christine E Larkins, Daniel M Grunberg, Gabriel M Daniels, Erik J Feldtmann, Martin J Cohn","doi":"10.1002/dvdy.70050","DOIUrl":"10.1002/dvdy.70050","url":null,"abstract":"<p><strong>Background: </strong>In eutherian mammals, the embryonic cloaca is partitioned into genitourinary and anorectal canals by the urorectal septum. In the mouse embryo, the urorectal septum contributes to the perineum, which separates the anus from the external genitalia. During the growth of the urorectal septum, endodermal epithelium of the cloaca is displaced to the surface of the perineum, where endodermal cells are integrated into the developing skin. However, it is unknown whether the endodermal lineage of the perineum acquires true epidermal identity, an enigmatic fate for endodermal cells.</p><p><strong>Results: </strong>We find that endodermal cells that reach the surface of the perineum express markers of basal, spinous, and granular epidermis. During postnatal development, the endodermal lineage of the perineum epidermis undergoes terminal differentiation and desquamation and is replaced by adjacent ectoderm. Live imaging and single-cell tracking show that ectodermal cells move at a faster velocity in a lateral-to-medial direction, indicating convergence toward the narrow band of endoderm that lies between the anus and external genitalia.</p><p><strong>Conclusions: </strong>Cloacal endoderm differentiates into a non-renewing, transient epidermis at the midline of the perineum. Differences in directionality and velocity of cell movement patterns between endodermal and ectodermal cells suggest that the perineum epidermis develops by convergent extension.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483555","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":"Combinatorial expression of glial transcription factors induces Schwann cell-specific gene expression in mouse embryonic fibroblasts.","authors":"Lauren Belfiore, Anjali Balakrishnan, Yacine Touahri, Dawn Zinyk, Humna Noman, Satoshi Okawa, Jeff Biernaskie, Carol Schuurmans","doi":"10.1002/dvdy.70054","DOIUrl":"10.1002/dvdy.70054","url":null,"abstract":"<p><strong>Background: </strong>Schwann cells provide peripheral nerve trophic support, myelinate axons, and assist in repair. However, Schwann cell repair capacity is limited by chronic injury, disease, and aging. Schwann cell reprogramming is a cellular conversion strategy that could provide a renewable cell supply to repair injured nerves. Here, we developed a plasmid-based approach to test the Schwann cell conversion potential of four glial transcription factors.</p><p><strong>Results: </strong>We employed four transcription factors implicated in Schwann cell differentiation and repair: Sox10, Sox2, Jun, and Pax3. Expression vectors were generated for Sox10 alone and two triple transcription factor combinations: Jun-Pax3-Sox2 (triple 1, T1) and Sox10-Jun-Sox2 (triple 2, T2). Mouse embryonic fibroblasts (MEFs) were transfected with these vectors, transferred to glial inductive media, and Schwann cell-marker expression was in assessed by immunostaining, flow cytometry, and qPCR. All expression vectors repressed fibroblast-specific gene expression. However, T2 was most efficient at generating O4⁺ Schwann cell-like cells, which had some capacity to myelinate denervated axons from explanted dorsal root ganglia. In comparison, T1 more efficiently induced repair Schwann cell-marker expression in converted O4⁺ cells.</p><p><strong>Conclusions: </strong>T1 and T2 convert MEFs to Schwann cells with different efficacies and gene expression profiles, and may provide cell-based therapies for peripheral nerve repair.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332577","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":"Genomic evolution of EGF-CFC genes in deuterostomes.","authors":"Natalia A Shylo, Paul A Trainor","doi":"10.1002/dvdy.70051","DOIUrl":"10.1002/dvdy.70051","url":null,"abstract":"<p><strong>Background: </strong>EGF-CFC proteins are a bilaterian innovation, but they are best known for their roles in Nodal signaling during gastrulation and left-right patterning in vertebrates. Species with multiple family members show evidence of functional specialization. For example, in mouse, Cripto is required for gastrulation, whereas CFC1 is involved in left-right patterning. However, members of the EGF-CFC family across model organisms exhibit limited sequence conservation beyond the EGF-CFC domain, posing challenges for determining their evolutionary history and functional conservation.</p><p><strong>Results: </strong>In this study, we describe the evolutionary history of the EGF-CFC family of proteins across several branches of deuterostomes, with a particular focus on vertebrates. We trace the EGF-CFC gene family from a single gene in the deuterostome ancestor through its expansion and functional specialization in tetrapods, and subsequent gene loss and translocation in eutherian mammals. Mouse Cripto and CFC1, zebrafish Tdgf1, and each Xenopus EGF-CFC gene (Tdgf1, Tdgf1.2 and Cripto.3) are all descendants of the ancestral deuterostome Tdgf1 gene.</p><p><strong>Conclusions: </strong>We propose that subsequent to EGF-CFC family expansion in tetrapods, Tdgf1B (Xenopus Tdgf1.2) acquired specialization in the left-right patterning cascade, and then after its translocation in eutherians to a different chromosomal location, CFC1 has maintained that specialization.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324707","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}