{"title":"An Lgr5-independent developmental lineage is involved in mouse intestinal regeneration.","authors":"Maryam Marefati, Valeria Fernandez-Vallone, Morgane Leprovots, Gabriella Vasile, Frédérick Libert, Anne Lefort, Gilles Dinsart, Achim Weber, Jasna Jetzer, Marie-Isabelle Garcia, Gilbert Vassart","doi":"10.1242/dev.204654","DOIUrl":"https://doi.org/10.1242/dev.204654","url":null,"abstract":"<p><p>Collagenase/dispase treatment of intestinal tissue from adult mice generates cells growing in matrigel as stably replatable cystic spheroids in addition to differentiated organoids. Contrary to classical EDTA-derived organoids, these spheroids display poor intestinal differentiation and are independent of Rspondin/Noggin/EGF for growth. Their transcriptome resembles strikingly that of fetal intestinal spheroids, with downregulation of crypt base columnar cell (CBC) markers (Lgr5, Ascl2, Smoc2, Olfm4). In addition, they display upregulation of inflammatory and mesenchymal genetic programs, together with robust expression of YAP target genes. Lineage tracing, cell-sorting and single cell RNA sequencing experiments demonstrate that adult spheroid-generating cells belong to a hitherto undescribed developmental lineage, independent of Lgr5+ve CBCs, and are involved in regeneration of the epithelium following CBC ablation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-02-15Epub Date: 2025-03-03DOI: 10.1242/dev.204514
Yonit Maroudas-Sacks, S Suganthan, Liora Garion, Yael Ascoli-Abbina, Ariel Westfried, Noam Dori, Iris Pasvinter, Marko Popović, Kinneret Keren
{"title":"Mechanical strain focusing at topological defect sites in regenerating Hydra.","authors":"Yonit Maroudas-Sacks, S Suganthan, Liora Garion, Yael Ascoli-Abbina, Ariel Westfried, Noam Dori, Iris Pasvinter, Marko Popović, Kinneret Keren","doi":"10.1242/dev.204514","DOIUrl":"10.1242/dev.204514","url":null,"abstract":"<p><p>The formation of a new head during Hydra regeneration involves the establishment of a head organizer that functions as a signaling center and contains an aster-shaped topological defect in the organization of the supracellular actomyosin fibers. Here, we show that the future head region in regenerating tissue fragments undergoes multiple instances of extensive stretching and rupture events from the onset of regeneration. These recurring localized tissue deformations arise due to transient contractions of the supracellular ectodermal actomyosin fibers that focus mechanical strain at defect sites. We further show that stabilization of aster-shaped defects is disrupted by perturbations of the Wnt signaling pathway. We propose a closed-loop feedback mechanism promoting head organizer formation, and develop a biophysical model of regenerating Hydra tissues that incorporates a morphogen source activated by mechanical strain and an alignment interaction directing fibers along morphogen gradients. We suggest that this positive-feedback loop leads to mechanical strain focusing at defect sites, enhancing local morphogen production and promoting robust organizer formation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-02-15Epub Date: 2025-02-17DOI: 10.1242/dev.202066
Camilla Mapstone, Berenika Plusa
{"title":"Machine learning approaches for image classification in developmental biology and clinical embryology.","authors":"Camilla Mapstone, Berenika Plusa","doi":"10.1242/dev.202066","DOIUrl":"10.1242/dev.202066","url":null,"abstract":"<p><p>The rapid increase in the amount of available biological data together with increasing computational power and innovative new machine learning algorithms has resulted in great potential for machine learning approaches to revolutionise image analysis in developmental biology and clinical embryology. In this Spotlight, we provide an introduction to machine learning for developmental biologists interested in incorporating machine learning techniques into their research. We give an overview of essential machine learning concepts and models and describe a few recent examples of how these techniques can be used in developmental biology. We also briefly discuss latest advancements in the field and how it might develop in the future.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dendritic cells in developing and adult zebrafish arise from different origins and display distinct flt3 dependencies.","authors":"Guanzhen Lin, Youqi Wang, Thi Giang Pham, Zilong Wen","doi":"10.1242/dev.204410","DOIUrl":"10.1242/dev.204410","url":null,"abstract":"<p><p>Dendritic cells (DCs) are key cellular components of the immune system and perform crucial functions in innate and acquired immunity. In mammals, it is generally believed that DCs originate exclusively from hematopoietic stem cells (HSCs). Using a temporal-spatial resolved fate-mapping system, here we show that, in zebrafish, DCs arise from two sources: dorsal aorta-born endothelium-derived hematopoietic progenitors (EHPs) and HSCs. The EHP-derived DCs emerge early, predominantly colonizing the developing thymus during larval stages and diminishing by juvenile stages. In contrast, HSC-derived DCs emerge later and can populate different tissues from late larval stages to adulthood. We further document that the EHP- and HSC-derived DCs display different dependencies on Fms-like tyrosine kinase 3 (Flt3), a pivotal receptor tyrosine kinase crucial for DC development in mammals. Our study reveals the presence of two distinct waves of DC development in zebrafish, each with unique origins and developmental controls.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-02-15Epub Date: 2025-03-03DOI: 10.1242/dev.204655
{"title":"The people behind the papers - Yonit Maroudas-Sacks and Marko Popović.","authors":"","doi":"10.1242/dev.204655","DOIUrl":"10.1242/dev.204655","url":null,"abstract":"<p><p>During Hydra regeneration, supracellular actomyosin fibres are disoriented at two distinct foci of the regenerating tissue. These sites of nematic topological defects eventually form the new head and foot of the regenerated animal. In a new study, Yonit Maroudas-Sacks, Marko Popović, Kinneret Keren and colleagues propose a positive-feedback loop that incorporates fibre organisation, tissue strain and morphogen gradients to promote head organiser formation. To find out more about the work, we caught up with first author Yonit Maroudas-Sacks and co-corresponding author Marko Popović, Group Leader at the Max Planck Institute for the Physics of Complex Systems, Germany.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-02-15Epub Date: 2025-02-17DOI: 10.1242/dev.204341
Aakriti Singh, Meike van den Burgh, Vigneshwarr Boopathy, Patrick van Nierop Y Sanchez, Josephine Bageritz, Ingrid Lohmann, Katrin Domsch
{"title":"Autonomous function of Antennapedia in adult muscle precursors directly connects Hox genes to adult muscle development.","authors":"Aakriti Singh, Meike van den Burgh, Vigneshwarr Boopathy, Patrick van Nierop Y Sanchez, Josephine Bageritz, Ingrid Lohmann, Katrin Domsch","doi":"10.1242/dev.204341","DOIUrl":"10.1242/dev.204341","url":null,"abstract":"<p><p>The evolutionarily conserved Hox genes define segment identities along the anterior-posterior axis and are expressed in most cell types within each segment, performing specific functions tailored to cellular needs. It has been suggested previously that Drosophila adult flight muscles in the second thoracic segment (T2) develop without direct Hox gene input, relying instead on ectodermal signals to shape their identity. However, our research, leveraging single-cell transcriptomics of Drosophila wing discs and Hox perturbation experiments using CRISPR technology and gain-of-function assays, unveiled a more intricate regulatory landscape. We found that the Hox protein Antennapedia (Antp) is essential for adult flight muscle development, acting in two crucial ways: by regulating the cell cycle rate of adult muscle precursors (AMPs) through repression of proliferation genes, and by guiding flight muscle fate via regulation of Hedgehog (Hh) signalling during cell fate establishment. Antp, along with its co-factor Apterous (Ap), directly interacts with the patched (ptc) locus to control its expression in AMPs. These findings challenge the notion of T2 as a 'Hox-free' zone, highlighting the indispensable role of low-level Antp expression in adult muscle development.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-02-15Epub Date: 2025-02-17DOI: 10.1242/dev.204458
Anupama Rao, Andrew Russell, Jose Segura-Bermudez, Charles Franz, Rejenae Dockery, Anton Blatnik, Jacob Panten, Mateo Zevallos, Carson McNulty, Maciej Pietrzak, Joseph Aaron Goldman
{"title":"A cardiac transcriptional enhancer is repurposed during regeneration to activate an anti-proliferative program.","authors":"Anupama Rao, Andrew Russell, Jose Segura-Bermudez, Charles Franz, Rejenae Dockery, Anton Blatnik, Jacob Panten, Mateo Zevallos, Carson McNulty, Maciej Pietrzak, Joseph Aaron Goldman","doi":"10.1242/dev.204458","DOIUrl":"10.1242/dev.204458","url":null,"abstract":"<p><p>Zebrafish have a high capacity to regenerate their hearts. Several studies have surveyed transcriptional enhancers to understand how gene expression is controlled during heart regeneration. We have identified REN (the runx1 enhancer) that, during regeneration, regulates the expression of the nearby runx1 gene. We show that runx1 mRNA is reduced with deletion of REN (ΔREN), and cardiomyocyte proliferation is enhanced in ΔREN mutants only during regeneration. Interestingly, in uninjured hearts, ΔREN mutants have reduced expression of adamts1, a nearby gene that encodes a Collagen protease. This results in excess Collagen within cardiac valves of uninjured hearts. The ΔREN Collagen phenotype is rescued by an allele with Δrunx1 mutations, suggesting that in uninjured hearts REN regulates adamts1 independently of runx1. Taken together, this suggests that REN is rewired from adamts1 in uninjured hearts to stimulate runx1 transcription during regeneration. Our data point to a previously unappreciated mechanism for gene regulation during zebrafish heart regeneration. We report that an enhancer is rewired from expression in a distal cardiac domain to activate a different gene in regenerating tissue.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-02-15Epub Date: 2025-02-20DOI: 10.1242/dev.204689
George Hunt, Ana Cvejic
{"title":"In preprints: insights into the regulation of haematopoietic stem cell emergence in vitro and in vivo.","authors":"George Hunt, Ana Cvejic","doi":"10.1242/dev.204689","DOIUrl":"https://doi.org/10.1242/dev.204689","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cdkn1c orchestrates a molecular network that regulates euploidy of male mouse germline stem cells.","authors":"Mito Kanatsu-Shinohara, Takuya Yamamoto, Tianjiao Liu, Keiichi I Nakayama, Takashi Shinohara","doi":"10.1242/dev.204286","DOIUrl":"10.1242/dev.204286","url":null,"abstract":"<p><p>Karyotype instability in the germline leads to infertility. Unlike the female germline, the male germline continuously produces fertile sperm throughout life. Here, we present a molecular network responsible for maintaining karyotype stability in the male mouse germline. Loss of the cyclin-dependent kinase inhibitor Cdkn1c in undifferentiated spermatogonia induced degeneration of spermatogenesis prior to entry into the differentiating spermatogonia stage. In vitro analysis of mouse spermatogonial stem cells revealed that CDKN1C localized to spindle microtubules during metaphase, and that disrupted microtubule dynamics increased its phosphorylation. Cdkn1c deficiency activated the spindle assembly checkpoint and led to centrosome amplification, premature chromosome segregation, and loss of AURKB, and ultimately TRP53-dependent apoptosis. Trp53-deficient spermatogonial stem cells exhibited karyotype defects, but proliferated normally despite reduced CDKN1C and AURKB expression. In contrast, Aurkb depletion upregulated TRP53 and CDKN1C, suggesting a negative feedback loop to maintain euploidy. Thus, Cdkn1c regulates the male germline karyotype.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-02-15Epub Date: 2025-02-17DOI: 10.1242/dev.204397
Bryana N Harris, Laura A Woo, R Noah Perry, Alexia M Wallace, Mete Civelek, Matthew J Wolf, Jeffrey J Saucerman
{"title":"Dynamic map illuminates Hippo-cMyc module crosstalk driving cardiomyocyte proliferation.","authors":"Bryana N Harris, Laura A Woo, R Noah Perry, Alexia M Wallace, Mete Civelek, Matthew J Wolf, Jeffrey J Saucerman","doi":"10.1242/dev.204397","DOIUrl":"10.1242/dev.204397","url":null,"abstract":"<p><p>Numerous regulators of cardiomyocyte (CM) proliferation have been identified, yet how they coordinate during cardiac development or regeneration is poorly understood. Here, we developed a computational model of the CM proliferation regulatory network to obtain key regulators and systems-level understanding. The model defines five modules (DNA replication, mitosis, cytokinesis, growth factor, Hippo pathway) and integrates them into a network of 72 nodes and 88 reactions that correctly predicts 74 of 81 (91.35%) independent experiments from the literature. The model predicts that in response to YAP activation, the Hippo module crosstalks to the growth factor module via PI3K and cMyc to drive cell cycle activity. This predicted YAP-cMyc axis is validated experimentally in rat CMs and further supported by YAP-stimulated cMyc open chromatin and mRNA in mouse hearts. This validated computational model predicts how individual regulators and modules coordinate to control CM proliferation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}