DevelopmentPub Date : 2025-10-15Epub Date: 2025-09-08DOI: 10.1242/dev.204813
Gat Rauner, Nicole C Traugh, Colin J Trepicchio, Meadow E Parrish, Kenan Mushayandebvu, Charlotte Kuperwasser
{"title":"Single-cell organogenesis captures complex breast tissue formation in three dimensions.","authors":"Gat Rauner, Nicole C Traugh, Colin J Trepicchio, Meadow E Parrish, Kenan Mushayandebvu, Charlotte Kuperwasser","doi":"10.1242/dev.204813","DOIUrl":"10.1242/dev.204813","url":null,"abstract":"<p><p>Current breast organoid models, primarily based on self-assembly, face limitations in accurately mimicking the complex stages of tissue development, notably in replicating detailed tissue architectures and cellular diversity. Here, we demonstrate that a solitary human breast stem cell can, within a controlled hydrogel extracellular matrix environment, autonomously generate niche signals that drive directed organogenesis, producing organoids with mesenchymal and parenchymal components. This system surpasses traditional models by forming complex, heterogeneous ductal-lobular structures akin to those in native human breast tissue with the emergence of mesenchyme-like stroma. Using long-term, high-resolution live imaging, we quantitatively analyze the dynamic tissue development and morphogenesis, capturing cellular behaviors crucial for understanding both development and disease. The inclusion of patient-derived cells from diverse biological backgrounds, including pre- and post-menopausal donors, significantly enhances the applicability of the model. Our findings underscore that this controlled organogenesis approach represents a major leap over existing methods, offering a robust platform for probing the intricacies of human breast tissue development and its responses to environmental cues.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788544","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 : 2025-10-15Epub Date: 2025-10-16DOI: 10.1242/dev.204762
Michael Zelko, Danyan Li, Sudheesh Allikka Parambil, Axel Poulet, Andrew Verdesca, Kaspar Mazeika, Krishnakali Dasgupta, Josien C van Wolfswinkel
{"title":"Enhanced RNA quality control maintains long-term regenerative ability in planarians.","authors":"Michael Zelko, Danyan Li, Sudheesh Allikka Parambil, Axel Poulet, Andrew Verdesca, Kaspar Mazeika, Krishnakali Dasgupta, Josien C van Wolfswinkel","doi":"10.1242/dev.204762","DOIUrl":"10.1242/dev.204762","url":null,"abstract":"<p><p>Planarians have proficient regenerative abilities that persist undiminished throughout adulthood, mediated by their stem cells (neoblasts). It is unclear how planarians accomplish this, as most animals show age-related declines in health and regeneration. Neoblasts express the conserved RNA regulatory PIWI protein SMEDWI-1, homologs of which are found in germ cells and long-lived cells in other systems. We previously found that loss of SMEDWI-1 from the neoblasts results in accumulation of non-coding and aberrant RNAs. Here, we report that, over time, SMEDWI-1-depleted animals develop defects in wound repair and regeneration, alterations in secreted proteins, and increased intracellular protein aggregation. Our data indicate that these defects result from misassembly of the signal recognition particle (SRP), a ribonucleoprotein (RNP) responsible for co-translational protein secretion that contains a non-coding RNA as a scaffold. In the absence of tight regulation of non-coding RNA, as provided by SMEDWI-1, gradual accumulation of RNAs leads to imbalances in essential cellular machinery such as the SRP, resulting in compromised proteostasis and progressive loss of organismal vigor.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069333","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 : 2025-10-15Epub Date: 2025-06-03DOI: 10.1242/dev.204610
Brady P Hammond, Sameera Zia, Eugene Hahn, Margarita Kapustina, Tristan Lange, Sarah Friesen, Rupali Manek, Kelly V Lee, Adrian Castellanos-Molina, Floriane Bretheau, Mark S Cembrowski, Bradley J Kerr, Steve Lacroix, Jason R Plemel
{"title":"CSF1R ligands promote microglial proliferation but are not the sole regulators of developmental microglial proliferation.","authors":"Brady P Hammond, Sameera Zia, Eugene Hahn, Margarita Kapustina, Tristan Lange, Sarah Friesen, Rupali Manek, Kelly V Lee, Adrian Castellanos-Molina, Floriane Bretheau, Mark S Cembrowski, Bradley J Kerr, Steve Lacroix, Jason R Plemel","doi":"10.1242/dev.204610","DOIUrl":"10.1242/dev.204610","url":null,"abstract":"<p><p>Microglia - the predominant immune cells of the brain and spinal cord - perform essential functions for the development and maintenance of the central nervous system, contingent upon the regulated developmental proliferation of microglia. However, the factor(s) that regulate microglial proliferation remain unclear. Here, we confirmed the timeline of developmental proliferation and used bioinformatics to identify potential signalling onto microglia in mouse from datasets collected at an age of high developmental microglial proliferation. Of the predicted factors, we found that colony stimulating factor 1 receptor (CSF1R) ligands boosted proliferation in vitro and were increasingly expressed in the brain across development with each displaying a distinct regional and temporal expression pattern. However, we did not observe a coincident alteration to CSF1R ligand levels in a model of abnormal developmental proliferation. Together, although CSF1R ligands can promote microglial proliferation in culture, their developmental expression patterns suggest that they function alongside other unknown factors to regulate developmental microglial proliferation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093051","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 : 2025-10-15Epub Date: 2025-07-11DOI: 10.1242/dev.204395
Dong Feng, Yanhan Dong, Yiran Song, Nicholas Yapundich, Yifang Xie, Brian Spurlock, Tingting Lyu, Landry Kuehn, Li Qian, Jiandong Liu
{"title":"Nr4a1 modulates inflammation and heart regeneration in zebrafish.","authors":"Dong Feng, Yanhan Dong, Yiran Song, Nicholas Yapundich, Yifang Xie, Brian Spurlock, Tingting Lyu, Landry Kuehn, Li Qian, Jiandong Liu","doi":"10.1242/dev.204395","DOIUrl":"10.1242/dev.204395","url":null,"abstract":"<p><p>Recent findings have highlighted the complex role of inflammation in zebrafish heart regeneration, demonstrating that although inflammation is essential for initiating transient fibrosis and tissue repair, chronic inflammation, and unresolved fibrosis, could impede full regenerative recovery. In this study, we identified the nuclear receptor Nr4a1 as a crucial regulator of this regenerative process in zebrafish. Loss of Nr4a1 function led to a prolonged and excessive inflammatory response, disrupted neutrophil migration, delayed fibrin clearance, and ultimately impaired heart regeneration. Transcriptome-wide RNA-seq analysis at different injury stages revealed molecular disruptions associated with dysregulated inflammation and fibrosis in nr4a1 mutants. Notably, partial inhibition of the pro-inflammatory cytokine Tnfα rescued heart regeneration in the nr4a1 mutants, highlighting the therapeutic potential of modulating inflammation. Our findings suggest that Nr4a1 plays a crucial role in orchestrating the immune response during heart regeneration and may serve as a valuable target for enhancing cardiac repair following injury.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483600","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 : 2025-10-15Epub Date: 2025-10-06DOI: 10.1242/dev.205227
{"title":"An interview with Meritxell (Meri) Huch.","authors":"","doi":"10.1242/dev.205227","DOIUrl":"https://doi.org/10.1242/dev.205227","url":null,"abstract":"<p><p>Meritxell (Meri) Huch is a Director and Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, where her group uses 3D organoid models to study the maintenance and repair of adult tissues, as well as the mechanisms by which their dysregulation contributes to disease. This year, Meri is a Guest Editor for Development's special issue on lifelong development, which highlights how developmental processes and pathways are used throughout animal lifespans. We caught up with Meri over Teams to discuss the importance of using organoid models to study tissue regeneration and pathology, as well as some of the most exciting research questions that her lab is trying to answer.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 20","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231811","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 : 2025-10-15Epub Date: 2025-06-17DOI: 10.1242/dev.204265
Berivan Temiz, Michael Meier, Megan J Wilson
{"title":"Single-cell transcriptomic profiling of the whole colony of Botrylloides diegensis: insights into tissue specialization and blastogenesis.","authors":"Berivan Temiz, Michael Meier, Megan J Wilson","doi":"10.1242/dev.204265","DOIUrl":"10.1242/dev.204265","url":null,"abstract":"<p><p>Botrylloides diegensis is a colonial ascidian that has been the focus of developmental, evolutionary and regeneration research. In this study, we performed single-cell RNA sequencing (scRNA-seq) of an entire B. diegensis colony, including zooids, buds and vascular tunics, to resolve cellular heterogeneity and to identify cell and tissue markers. We identified 29 major cell clusters within the colony and used in situ hybridization to examine the spatial expression of cluster marker genes. Numerous tissue types were identified at the molecular level, including blood cells and zooid tissues, such as the branchial epithelium, stomach and endostyle. Distinct cluster markers were identified for specific regions of the stomach epithelium, highlighting the specialization of these regions and the strength of using scRNA-seq to explore their functionality. Cell trajectory projections highlighted the early appearance of progenitor clusters, whereas more differentiated zooid-related tissues appeared later in the developmental path. This study provides a valuable resource for understanding the development, tissue function and regeneration of B. diegensis. It demonstrates the power of scRNA-seq to define cell types and tissues in complex colonial organisms.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126852","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 : 2025-10-15Epub Date: 2025-10-16DOI: 10.1242/dev.204668
Yochabed Miliard, Shannon Moreno, Lauren E Cote, Peter W Reddien
{"title":"egal-1 and microtubules promote regeneration polarity in planarians.","authors":"Yochabed Miliard, Shannon Moreno, Lauren E Cote, Peter W Reddien","doi":"10.1242/dev.204668","DOIUrl":"https://doi.org/10.1242/dev.204668","url":null,"abstract":"<p><p>A central problem in regeneration is how the identity of new tissues is specified. A classic example is the head-versus-tail regeneration decision in planarians. notum is wound induced at anterior-facing planarian wounds, where it triggers head regeneration through inhibition of canonical Wnt signaling. This represents the earliest known asymmetric regeneration step between anterior- and posterior-facing wounds. Wound-induced notum is specific to longitudinal (anterior-posterior-axis oriented) muscle cells, suggesting these fibers might harbor polarity harnessed for the head-tail regeneration decision. The processes that occur within longitudinal muscle after injury for preferential notum activation at anterior-facing wounds are poorly understood. We utilized single-cell RNA sequencing to identify multiple wound-induced genes in longitudinal muscle cells and identified processes required for wound-induced notum asymmetry. Egalitarian-like-1 (Egal-1) is wound induced in longitudinal muscle and has some domain similarity with Drosophila Egalitarian, which facilitates asymmetric RNA localization. Both egal-1 RNAi animals and animals with destabilized microtubules (via colchicine or nocodazole treatment) show ectopic notum expression at posterior-facing wounds. We suggest that Egal-1 and microtubules are together required for longitudinal muscle fibers to promote planarian regeneration polarity.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 20","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299214","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 : 2025-10-15Epub Date: 2025-07-30DOI: 10.1242/dev.204790
Amruta Tendolkar, Mayssa H Mokalled
{"title":"Mechanisms underpinning spontaneous spinal cord regeneration.","authors":"Amruta Tendolkar, Mayssa H Mokalled","doi":"10.1242/dev.204790","DOIUrl":"10.1242/dev.204790","url":null,"abstract":"<p><p>Vertebrates exhibit a range of regenerative capacities following spinal cord injury. At one end of the spectrum are chief regenerators, including teleost fish and urodele amphibians. At the other end, most mammalian species exhibit limited repair and multicellular complications following spinal cord injury. Pro-regenerative immune, glial and neuronal injury responses underlie innate spinal cord repair in highly regenerative vertebrates. In many instances, fundamental mechanisms of spinal cord repair represent ancestral neuroprotection mechanisms that are conserved but become overwhelmed by anti-regenerative effects in mammals. Reflecting recent advances in the field, we review how fine-tuned immune responses, pro-regenerative glial cell reactivity and multimodal neuronal repair direct innate spinal cord repair.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 20","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741626","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 : 2025-10-15Epub Date: 2025-09-08DOI: 10.1242/dev.204632
John W Quinn, Mariah C Lee, Chloe Van Hazel, Melissa A Wilson, Robin E Harris
{"title":"A threshold level of JNK activates damage-responsive enhancers via JAK/STAT to promote tissue regeneration.","authors":"John W Quinn, Mariah C Lee, Chloe Van Hazel, Melissa A Wilson, Robin E Harris","doi":"10.1242/dev.204632","DOIUrl":"10.1242/dev.204632","url":null,"abstract":"<p><p>Tissue regeneration requires precise activation and coordination of genes, many of which are reused from development. Although key factors have been identified, how their expression is initiated and spatially regulated after injury remains unclear. The stress-activated MAP kinase JNK is a conserved driver of regeneration and promotes expression of genes involved in proliferation, growth and cell fate changes in Drosophila. However, how JNK selectively activates its targets in damaged tissue is not well understood. We have previously identified damage-responsive, maturity-silenced (DRMS) enhancers as JNK-activated elements that are crucial for regeneration. Here, we show that cell death is dispensable for the activation of these enhancers, which only depend on JNK and its immediate downstream effectors. One of these is JAK/STAT, which acts as a direct, additional input necessary to expand enhancer activity into the wound periphery where JNK alone is insufficient. Furthermore, we demonstrate that a threshold level of JNK is required to initiate enhancer activation. Together, our findings reveal how JNK and JAK/STAT signaling cooperate to drive spatially and temporally regulated gene expression through damage-responsive enhancers, ensuring proper regenerative outcomes.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793720","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 : 2025-10-15Epub Date: 2025-10-16DOI: 10.1242/dev.205116
Griffen Wakelin, Adam P W Johnston
{"title":"Regulation of tissue regeneration and repair by the peripheral nervous system.","authors":"Griffen Wakelin, Adam P W Johnston","doi":"10.1242/dev.205116","DOIUrl":"https://doi.org/10.1242/dev.205116","url":null,"abstract":"<p><p>Amphibians display a remarkable capacity for tissue regeneration, with some able to regrow entire limbs. In mammals, while tissues such as skin, bones and skeletal muscles are capable of repair following injury, true multilineage regeneration is rare and restricted to the distal region of the digit tip. Although the mechanisms governing successful tissue repair and regeneration are still coming to light, it is now appreciated that innervation by local nerves is a necessary component of the regenerative microenvironment. In this Review, we examine the current state of the literature that identifies the role of axon-derived signals, Schwann cells and nerve-derived mesenchymal cells as direct and indirect supporters of tissue repair and regeneration. We will also discuss how these cells function under pathological conditions or situations of aberrant tissue repair. Altogether, these findings underscore the significance of elucidating the role of the peripheral nervous system in tissue homeostasis and repair, with potential implications for the development of targeted therapeutic interventions and regenerative medicine strategies.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 20","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307227","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}