IF 3.7 2区生物学

Development Pub Date : 2024-11-05 DOI: 10.1242/dev.202941

Joseph Lee, Antoine Gleizes, Nicolas V Janto, Lito L Appell, Siyang Sun, Felipe Takaesu, Sarah F Webster, Taylor Hailstock, Nick Barker, Adam D Gracz

{"title":"Lgr5+ intestinal stem cells are required for organoid survival after genotoxic injury.","authors":"Joseph Lee, Antoine Gleizes, Nicolas V Janto, Lito L Appell, Siyang Sun, Felipe Takaesu, Sarah F Webster, Taylor Hailstock, Nick Barker, Adam D Gracz","doi":"10.1242/dev.202941","DOIUrl":"10.1242/dev.202941","url":null,"abstract":"Progenitors and mature cells can maintain the intestinal epithelium by dedifferentiation and facultative intestinal stem cell (fISC) function when active ISCs (aISCs) are lost to damage. Here, we modeled fISC activation in intestinal organoids with doxorubicin (DXR), a chemotherapeutic known to ablate Lgr5+ aISCs in vivo. Similar fISC gene activation was observed between organoids treated with low vs high DXR, despite significantly decreased survival at the higher dose. aISCs exhibit dose-dependent loss after DXR but survive at doses compatible with organoid survival. We ablated residual aISCs after DXR using a Lgr52A-DTR allele and observed that aISC survival of the initial genotoxic insult is required for organoid survival following DXR. These results suggest that while typical fISC genes are activated by DXR injury in organoids, functional stemness remains dependent on the aISC pool. Finally, we show that human intestinal organoids require higher doses of DXR to induce loss of survival and downregulation of LGR5. Our data establish a reproducible model of DXR injury in intestinal organoids and reveal differences in in vitro responses to an established in vivo damage modality.","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582277","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}

引用次数: 0

Contributions of the Dachsous intracellular domain to Dachsous-Fat signaling. Dachsous 细胞内结构域对 Dachsous-Fat 信号转导的贡献。

IF 3.7 2区生物学

Development Pub Date : 2024-11-05 DOI: 10.1242/dev.202919

Bipin Kumar Tripathi, Kenneth D Irvine

{"title":"Contributions of the Dachsous intracellular domain to Dachsous-Fat signaling.","authors":"Bipin Kumar Tripathi, Kenneth D Irvine","doi":"10.1242/dev.202919","DOIUrl":"10.1242/dev.202919","url":null,"abstract":"The protocadherins Fat and Dachsous regulate organ growth, shape, patterning, and planar cell polarity. Although Dachsous and Fat have been described as ligand and receptor, respectively, in a signal transduction pathway, there is also evidence for bidirectional signaling. Here we assess signaling downstream of Dachsous through analysis of its intracellular domain. Genomic deletions of conserved sequences within dachsous identified regions of the intracellular domain that contribute to Ds activity. Deletion of the A motif increased Dachsous protein levels and decreased wing size. Deletion of the D motif decreased Dachsous levels at cell membranes, increased wing size, and disrupted wing, leg and hindgut patterning and planar cell polarity. Co-immunoprecipitation experiments established that the D motif is necessary and sufficient for association of Dachsous with key partners including Lowfat, Dachs, Spiny-legs, Fat and MyoID. Subdivision of the D motif identified distinct regions that preferentially contribute to different Ds activities. Our results identify motifs that are essential for Dachsous function and are consistent with the hypothesis that the key function of Dachsous is regulation of Fat.","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582270","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}

引用次数: 0

MRCK-1 activates non-muscle myosin for outgrowth of a unicellular tube in Caenorhabditis elegans. MRCK-1 激活非肌肉肌球蛋白，促进秀丽隐杆线虫单细胞管的生长。

IF 3.7 2区生物学

Development Pub Date : 2024-11-04 DOI: 10.1242/dev.202772

Evelyn M Popiel, Rhea Ahluwalia, Stefan Schuetz, Bin Yu, W Brent Derry

引用次数: 0

Retinal ganglion cell-derived semaphorin 6A segregates starburst amacrine cell dendritic scaffolds to organize the inner retina. 视网膜神经节细胞衍生的半aphorin 6A 可分离星形闪烁的羊膜细胞树突支架，从而组织内视网膜。

IF 3.7 2区生物学

Development Pub Date : 2024-11-04 DOI: 10.1242/dev.204293

Rebecca E James, Natalie R Hamilton, Lola Nicole Huffman, Victoria N Neckles, R. Jeroen Pasterkamp, Loyal A Goff, Alex L Kolodkin

{"title":"Retinal ganglion cell-derived semaphorin 6A segregates starburst amacrine cell dendritic scaffolds to organize the inner retina.","authors":"Rebecca E James, Natalie R Hamilton, Lola Nicole Huffman, Victoria N Neckles, R. Jeroen Pasterkamp, Loyal A Goff, Alex L Kolodkin","doi":"10.1242/dev.204293","DOIUrl":"10.1242/dev.204293","url":null,"abstract":"To form functional circuits, neurons must settle in their appropriate cellular locations and then project and elaborate neurites to contact their target synaptic neuropils. Laminar organization within the vertebrate retinal inner plexiform layer (IPL) facilitates pre- and postsynaptic neurite targeting, yet the precise mechanisms underlying establishment of functional IPL subdomains are not well understood. Here we explore mechanisms defining the compartmentalization of OFF and ON neurites generally, and OFF and ON direction-selective neurites specifically, within the developing IPL. We show that semaphorin 6A (Sema6A), a repulsive axon guidance cue, is required for delineation of OFF versus ON circuits within the IPL: in the Sema6a null IPL, the boundary between OFF and ON domains is blurred. Furthermore, Sema6A expressed by retinal ganglion cells (RGCs) directs laminar segregation of OFF and ON starburst amacrine cell (SAC) dendritic scaffolds, which themselves serve as a substrate upon which other retinal neurites elaborate. These results demonstrate that RGCs, the first neuron-type born within the retina, play an active role in functional specialization of the IPL.","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575560","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}

引用次数: 0

A genome engineered tool set for Drosophila TGF-β/BMP signaling studies. 用于果蝇 TGF-β/BMP 信号研究的基因组工程工具集。

IF 3.7 2区生物学

Development Pub Date : 2024-11-04 DOI: 10.1242/dev.204222

Clara-Maria Ell, Abu Safyan, Mrinal Chayengia, Manuela M M Kustermann, Jennifer Lorenz, Melanie Schächtle, George Pyrowolakis

{"title":"A genome engineered tool set for Drosophila TGF-β/BMP signaling studies.","authors":"Clara-Maria Ell, Abu Safyan, Mrinal Chayengia, Manuela M M Kustermann, Jennifer Lorenz, Melanie Schächtle, George Pyrowolakis","doi":"10.1242/dev.204222","DOIUrl":"https://doi.org/10.1242/dev.204222","url":null,"abstract":"Ligands of the TGF-β/BMP superfamily are critically involved in the regulation of growth, patterning and organogenesis and can act as long-range morphogens. Essential for understanding TGF-β/BMP signaling dynamics and regulation are tools that allow monitoring and manipulating pathway components expressed at physiological levels and endogenous spatiotemporal patterns. We used genome engineering to generate a comprehensive library of endogenously epitope- or fluorescently-tagged versions of receptors, co-receptors, transcription factors and key feedback regulators of the Drosophila BMP and Activin signaling pathways. We demonstrate that the generated alleles are biologically active and can be utilized for assessing tissue and subcellular distribution of the corresponding proteins. Further, we show that the genomic platforms can be used for in locus structure-function and cis-regulatory analyses. Finally, we present a complementary set of protein binder-based tools, which allow visualization as well as manipulation of the stability and subcellular localization of epitope-tagged proteins, providing new tools for the analysis of BMP signaling and beyond.","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567939","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}

引用次数: 0

The GTPase RAB6 is required for stem cell maintenance and cell migration in the gut epithelium. 肠道上皮细胞的干细胞维持和细胞迁移需要 GTPase RAB6。

IF 3.7 2区生物学

Development Pub Date : 2024-11-01 Epub Date: 2024-10-21 DOI: 10.1242/dev.203038

Pierre Simonin, Gehenna Lobo Guerrero, Sabine Bardin, Ram Venkata Gannavarapu, Denis Krndija, Joseph Boyd, Stephanie Miserey, Danijela Matic Vignjevic, Bruno Goud

{"title":"The GTPase RAB6 is required for stem cell maintenance and cell migration in the gut epithelium.","authors":"Pierre Simonin, Gehenna Lobo Guerrero, Sabine Bardin, Ram Venkata Gannavarapu, Denis Krndija, Joseph Boyd, Stephanie Miserey, Danijela Matic Vignjevic, Bruno Goud","doi":"10.1242/dev.203038","DOIUrl":"10.1242/dev.203038","url":null,"abstract":"Intestinal epithelial cells, which are instrumental in nutrient absorption, fluid regulation, and pathogen defense, undergo continuous proliferation and differentiation within the intestinal crypts, migrating towards the luminal surface where they are eventually shed. RAB GTPases are key regulators of intracellular vesicular trafficking and are involved in various cellular processes, including cell migration and polarity. Here, we investigated the role of RAB6 in the development and maintenance of the gut epithelium. We generated conditional knockout mice with RAB6 specifically deleted in the gut epithelium. We found that deletion of the Rab6a gene resulted in embryonic lethality. In adult mice, RAB6 depletion led to altered villus architecture and impaired junction integrity without affecting the segregation of apical and basolateral membrane domains. Further, RAB6 depletion slowed down cell migration and adversely affected both cell proliferation and stem cell maintenance. Notably, the absence of RAB6 resulted in a diminished number of functional stem cells, as evidenced by the rapid death of isolated crypts from Rab6a KO mice when cultured as 3D organoids. Together, these results underscore the essential role of RAB6 in maintaining gut epithelial homeostasis.","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460573","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}

引用次数: 0

Transitions in development - an interview with Dorit Hockman. 发展中的过渡--采访 Dorit Hockman。

IF 3.7 2区生物学

Development Pub Date : 2024-11-01 Epub Date: 2024-10-22 DOI: 10.1242/dev.204444

引用次数: 0

Planar cell polarity zebrafish models of congenital scoliosis reveal underlying defects in notochord morphogenesis. 先天性脊柱侧凸的平面细胞极性斑马鱼模型揭示了脊索形态发生的新的潜在缺陷。

IF 3.7 2区生物学

Development Pub Date : 2024-11-01 Epub Date: 2024-11-12 DOI: 10.1242/dev.202829

Mingqin Wang, Sen Zhao, Chenjun Shi, Marie-Claude Guyot, Meijiang Liao, Josephine T Tauer, Bettina M Willie, Nikita Cobetto, Carl-Éric Aubin, Elke Küster-Schöck, Pierre Drapeau, Jitao Zhang, Nan Wu, Zoha Kibar

{"title":"Planar cell polarity zebrafish models of congenital scoliosis reveal underlying defects in notochord morphogenesis.","authors":"Mingqin Wang, Sen Zhao, Chenjun Shi, Marie-Claude Guyot, Meijiang Liao, Josephine T Tauer, Bettina M Willie, Nikita Cobetto, Carl-Éric Aubin, Elke Küster-Schöck, Pierre Drapeau, Jitao Zhang, Nan Wu, Zoha Kibar","doi":"10.1242/dev.202829","DOIUrl":"10.1242/dev.202829","url":null,"abstract":"Congenital scoliosis (CS) is a type of vertebral malformation for which the etiology remains elusive. The notochord is pivotal for vertebrae development, but its role in CS is still understudied. Here, we generated a zebrafish knockout of ptk7a, a planar cell polarity (PCP) gene that is essential for convergence and extension (C&E) of the notochord, and detected congenital scoliosis-like vertebral malformations (CVMs). Maternal zygotic ptk7a mutants displayed severe C&E defects of the notochord. Excessive apoptosis occurred in the malformed notochord, causing a significantly reduced number of vacuolated cells, and compromising the mechanical properties of the notochord. The latter manifested as a less-stiff extracellular matrix along with a significant reduction in the number of the caveolae and severely loosened intercellular junctions in the vacuolated region. These defects led to focal kinks, abnormal mineralization, and CVMs exclusively at the anterior spine. Loss of function of another PCP gene, vangl2, also revealed excessive apoptosis in the notochord associated with CVMs. This study suggests a new model for CS pathogenesis that is associated with defects in notochord C&E and highlights an essential role of PCP signaling in vertebrae development.","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460557","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}

引用次数: 0

Evolution and development of complex floral displays. 复杂花卉展示的进化和发展。

IF 3.7 2区生物学

Development Pub Date : 2024-11-01 Epub Date: 2024-11-05 DOI: 10.1242/dev.203027

Farahnoz N Khojayori, Udhaya Ponraj, Kristina Buch, Yi Zhao, Humberto Herrera-Ubaldo, Beverley J Glover

{"title":"Evolution and development of complex floral displays.","authors":"Farahnoz N Khojayori, Udhaya Ponraj, Kristina Buch, Yi Zhao, Humberto Herrera-Ubaldo, Beverley J Glover","doi":"10.1242/dev.203027","DOIUrl":"https://doi.org/10.1242/dev.203027","url":null,"abstract":"Flowering plants - angiosperms - display an astounding diversity of floral features, which have evolved in response to animal pollination and have resulted in the most species-rich plant clade. Combinations of macroscale (e.g. colour, symmetry, organ number) and microscale (e.g. cell type, tissue patterning) features often lead to highly elaborate floral displays. Most studies have focused on model species with simple floral displays to uncover the genetic and evolutionary mechanisms involved in flower evolution, yet few studies have focused on complex floral displays. Here, we review current knowledge on the development and evolution of complex floral displays. We review gene regulatory networks involved in four developmental pathways contributing to overall floral display (inflorescence architecture, organ identity, flower symmetry and flower colour) in classical plant models. We then discuss how evolutionary modification of one or more of these pathways has resulted in the production of a range of complex floral displays. Finally, we explore modular systems in which multiple pathways have been modified simultaneously, generating the most elaborate floral displays.","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582299","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}

引用次数: 0

Nuclear instance segmentation and tracking for preimplantation mouse embryos. 植入前小鼠胚胎的核实例分割和跟踪。

IF 3.7 2区生物学

Development Pub Date : 2024-11-01 Epub Date: 2024-11-06 DOI: 10.1242/dev.202817

Hayden Nunley, Binglun Shao, David Denberg, Prateek Grover, Jaspreet Singh, Maria Avdeeva, Bradley Joyce, Rebecca Kim-Yip, Abraham Kohrman, Abhishek Biswas, Aaron Watters, Zsombor Gal, Alison Kickuth, Madeleine Chalifoux, Stanislav Y Shvartsman, Lisa M Brown, Eszter Posfai

{"title":"Nuclear instance segmentation and tracking for preimplantation mouse embryos.","authors":"Hayden Nunley, Binglun Shao, David Denberg, Prateek Grover, Jaspreet Singh, Maria Avdeeva, Bradley Joyce, Rebecca Kim-Yip, Abraham Kohrman, Abhishek Biswas, Aaron Watters, Zsombor Gal, Alison Kickuth, Madeleine Chalifoux, Stanislav Y Shvartsman, Lisa M Brown, Eszter Posfai","doi":"10.1242/dev.202817","DOIUrl":"10.1242/dev.202817","url":null,"abstract":"For investigations into fate specification and morphogenesis in time-lapse images of preimplantation embryos, automated 3D instance segmentation and tracking of nuclei are invaluable. Low signal-to-noise ratio, high voxel anisotropy, high nuclear density, and variable nuclear shapes can limit the performance of segmentation methods, while tracking is complicated by cell divisions, low frame rates, and sample movements. Supervised machine learning approaches can radically improve segmentation accuracy and enable easier tracking, but they often require large amounts of annotated 3D data. Here, we first report a previously unreported mouse line expressing near-infrared nuclear reporter H2B-miRFP720. We then generate a dataset (termed BlastoSPIM) of 3D images of H2B-miRFP720-expressing embryos with ground truth for nuclear instances. Using BlastoSPIM, we benchmark seven convolutional neural networks and identify Stardist-3D as the most accurate instance segmentation method. With our BlastoSPIM-trained Stardist-3D models, we construct a complete pipeline for nuclear instance segmentation and lineage tracking from the eight-cell stage to the end of preimplantation development (>100 nuclei). Finally, we demonstrate the usefulness of BlastoSPIM as pre-train data for related problems, both for a different imaging modality and for different model systems.","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380273","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}

引用次数: 0

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