Pub Date : 2024-11-25DOI: 10.1016/j.devcel.2024.10.015
Yiqun Wang, Jialin Liu, Lucia Y. Du, Jannik L. Wyss, Jeffrey A. Farrell, Alexander F. Schier
During differentiation, cells become structurally and functionally specialized, but comprehensive views of the underlying remodeling processes are elusive. Here, we leverage single-cell RNA sequencing (scRNA-seq) developmental trajectories to reconstruct differentiation using two secretory tissues as models—the zebrafish notochord and hatching gland. First, we integrated expression and functional similarities to identify gene modules, revealing dozens of modules representing known and newly associated differentiation processes and their dynamics. Second, we focused on the unfolded protein response (UPR) transducer module to study how general versus cell-type-specific secretory functions are regulated. Profiling loss- and gain-of-function embryos identified that the UPR transcription factors creb3l1, creb3l2, and xbp1 are master regulators of a general secretion program. creb3l1/creb3l2 additionally activate an extracellular matrix secretion program, while xbp1 partners with bhlha15 to activate a gland-like secretion program. Our study presents module identification via multi-source integration for reconstructing differentiation (MIMIR) and illustrates how transcription factors confer general and specialized cellular functions.
{"title":"Gene module reconstruction identifies cellular differentiation processes and the regulatory logic of specialized secretion in zebrafish","authors":"Yiqun Wang, Jialin Liu, Lucia Y. Du, Jannik L. Wyss, Jeffrey A. Farrell, Alexander F. Schier","doi":"10.1016/j.devcel.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.015","url":null,"abstract":"During differentiation, cells become structurally and functionally specialized, but comprehensive views of the underlying remodeling processes are elusive. Here, we leverage single-cell RNA sequencing (scRNA-seq) developmental trajectories to reconstruct differentiation using two secretory tissues as models—the zebrafish notochord and hatching gland. First, we integrated expression and functional similarities to identify gene modules, revealing dozens of modules representing known and newly associated differentiation processes and their dynamics. Second, we focused on the unfolded protein response (UPR) transducer module to study how general versus cell-type-specific secretory functions are regulated. Profiling loss- and gain-of-function embryos identified that the UPR transcription factors <em>creb3l1</em>, <em>creb3l2</em>, and <em>xbp1</em> are master regulators of a general secretion program. <em>creb3l1/creb3l2</em> additionally activate an extracellular matrix secretion program, while <em>xbp1</em> partners with <em>bhlha15</em> to activate a gland-like secretion program. Our study presents module identification via multi-source integration for reconstructing differentiation (MIMIR) and illustrates how transcription factors confer general and specialized cellular functions.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"19 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Plants demonstrate a high degree of developmental plasticity, capable of regenerating entire individuals from detached somatic tissues—a regenerative phenomenon rarely observed in metazoa. Consequently, elucidating the lineage relationship between somatic founder cells and descendant cells in regenerated plant organs has long been a pursuit. In this study, we developed and optimized both DNA barcode- and multi-fluorescence-based cell-lineage tracing toolsets, employing an inducible method to mark individual cells in Arabidopsis donor somatic tissues at the onset of regeneration. Utilizing these complementary methods, we scrutinized cell identities at the single-cell level and presented compelling evidence that all cells in the regenerated Arabidopsis plants, irrespective of their organ types, originated from a single progenitor cell in the donor somatic tissue. Our discovery suggests a single-cell passage directing the transition from multicellular donor tissue to regenerated plants, thereby creating opportunities for cell-cell competition during plant regeneration—a strategy for maximizing survival.
植物具有高度的发育可塑性，能够从分离的体细胞组织再生出完整的个体--这种再生现象在中生代动物中很少见。因此，阐明再生植物器官中体细胞创始细胞和后代细胞之间的世系关系一直是人们追求的目标。在本研究中，我们开发并优化了基于 DNA 条形码和多重荧光的细胞系追踪工具集，采用诱导方法在再生开始时标记拟南芥供体体细胞组织中的单个细胞。利用这些互补方法，我们在单细胞水平上仔细研究了细胞特性，并提出了令人信服的证据，证明再生拟南芥植株中的所有细胞，无论其器官类型如何，都源自供体体细胞中的单个祖细胞。我们的发现表明，单细胞通道引导着从多细胞供体组织到再生植物的过渡，从而为植物再生过程中的细胞竞争创造了机会--这是一种最大限度提高存活率的策略。
{"title":"Development of an inducible DNA barcoding system to understand lineage changes in Arabidopsis regeneration","authors":"Xinyue Lu, Qiyan Zhang, Zejia Wang, Xuanzhi Cheng, Huiru Yan, Shuyi Cai, Huawei Zhang, Qikun Liu","doi":"10.1016/j.devcel.2024.10.023","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.023","url":null,"abstract":"Plants demonstrate a high degree of developmental plasticity, capable of regenerating entire individuals from detached somatic tissues—a regenerative phenomenon rarely observed in metazoa. Consequently, elucidating the lineage relationship between somatic founder cells and descendant cells in regenerated plant organs has long been a pursuit. In this study, we developed and optimized both DNA barcode- and multi-fluorescence-based cell-lineage tracing toolsets, employing an inducible method to mark individual cells in <em>Arabidopsis</em> donor somatic tissues at the onset of regeneration. Utilizing these complementary methods, we scrutinized cell identities at the single-cell level and presented compelling evidence that all cells in the regenerated <em>Arabidopsis</em> plants, irrespective of their organ types, originated from a single progenitor cell in the donor somatic tissue. Our discovery suggests a single-cell passage directing the transition from multicellular donor tissue to regenerated plants, thereby creating opportunities for cell-cell competition during plant regeneration—a strategy for maximizing survival.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"8 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.devcel.2024.10.022
Qinghui Mu, Andrew Ha, Antonio J.M. Santos, Yuan-Hung Lo, Vincent van Unen, Yi Miao, Madeline Tomaske, Veronica K. Guzman, Samira Alwahabi, Jenny J. Yuan, Lu Deng, Linheng Li, K. Christopher Garcia, Calvin J. Kuo
The rapidly regenerating intestinal epithelium requires crypt intestinal stem cells (ISCs). Wnt/β-catenin signaling maintains crypt homeostasis and Lgr5+ ISCs, and WNT ligands bind Frizzled receptors (FZD1–10). Identifying specific FZD(s) essential for intestinal homeostasis has been elusive; however, bioengineered antagonists blocking Wnt binding to FZD5 and FZD8 deplete the gut epithelium in vivo, highlighting potential roles. Here, an epithelial-specific Fzd5 knockout (KO) elicited lethal pan-intestinal crypt and villus loss, whereas an Lgr5+ ISC-specific Fzd5 KO depleted Lgr5+ ISCs via premature differentiation and repressed Wnt target genes. Fzd5-null phenotypes were rescued by constitutive β-catenin activation in vivo and in both mouse and human enteroids. KO of Fzd5, not Fzd8, in enteroids ablated responsiveness to dual-specificity FZD5/FZD8-selective Wnt surrogate agonists, which ameliorated DSS-induced colitis in wild-type and Fzd8 KO mice. Overall, FZD5 is a dominant and essential regulator of crypt homeostasis, Lgr5+ ISCs, and intestinal response to Wnt surrogate agonists, with implications for therapeutic mucosal repair.
{"title":"FZD5 controls intestinal crypt homeostasis and colonic Wnt surrogate agonist response","authors":"Qinghui Mu, Andrew Ha, Antonio J.M. Santos, Yuan-Hung Lo, Vincent van Unen, Yi Miao, Madeline Tomaske, Veronica K. Guzman, Samira Alwahabi, Jenny J. Yuan, Lu Deng, Linheng Li, K. Christopher Garcia, Calvin J. Kuo","doi":"10.1016/j.devcel.2024.10.022","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.022","url":null,"abstract":"The rapidly regenerating intestinal epithelium requires crypt intestinal stem cells (ISCs). Wnt/β-catenin signaling maintains crypt homeostasis and Lgr5+ ISCs, and WNT ligands bind Frizzled receptors (FZD1–10). Identifying specific FZD(s) essential for intestinal homeostasis has been elusive; however, bioengineered antagonists blocking Wnt binding to FZD5 and FZD8 deplete the gut epithelium <em>in vivo</em>, highlighting potential roles. Here, an epithelial-specific <em>Fzd5</em> knockout (KO) elicited lethal pan-intestinal crypt and villus loss, whereas an Lgr5+ ISC-specific <em>Fzd5</em> KO depleted Lgr5+ ISCs via premature differentiation and repressed Wnt target genes. Fzd5-null phenotypes were rescued by constitutive β-catenin activation <em>in vivo</em> and in both mouse and human enteroids. KO of <em>Fzd5</em>, not <em>Fzd8</em>, in enteroids ablated responsiveness to dual-specificity FZD5/FZD8-selective Wnt surrogate agonists, which ameliorated DSS-induced colitis in wild-type and <em>Fzd8</em> KO mice. Overall, FZD5 is a dominant and essential regulator of crypt homeostasis, Lgr5+ ISCs, and intestinal response to Wnt surrogate agonists, with implications for therapeutic mucosal repair.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"23 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.devcel.2024.10.021
Lu Deng, Xi C. He, Shiyuan Chen, Ning Zhang, Fengyan Deng, Allison Scott, Yanfeng He, Dai Tsuchiya, Sarah E. Smith, Michael Epp, Seth Malloy, Fang Liu, Mark Hembree, Qinghui Mu, Jeffrey S. Haug, Ermanno Malagola, Huzaifa Hassan, Kaitlyn Petentler, Rhonda Egidy, Lucinda Maddera, Linheng Li
The homeostasis of the intestinal epithelium relies on intricate yet insufficiently understood mechanisms of intestinal epithelial plasticity. Here, we elucidate the pivotal role of Frizzled5 (Fzd5), a Wnt pathway receptor, as a determinant of murine intestinal epithelial cell fate. Deletion of Fzd5 in Lgr5+ intestinal stem cells (ISCs) impairs their self-renewal, whereas its deletion in Krt19+ cells disrupts lineage generation, without affecting crypt integrity in either case. However, a broader deletion of Fzd5 across the epithelium leads to substantial crypt deterioration. Integrated analysis of single-cell RNA sequencing (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) identifies that Fzd5 governs chromatin accessibility, orchestrating the regulation of stem- and lineage-related gene expression mainly in ISCs and progenitor cells. In summary, our findings provide insights into the regulatory role of Fzd5 in governing intestinal epithelial plasticity.
{"title":"Frizzled5 controls murine intestinal epithelial cell plasticity through organization of chromatin accessibility","authors":"Lu Deng, Xi C. He, Shiyuan Chen, Ning Zhang, Fengyan Deng, Allison Scott, Yanfeng He, Dai Tsuchiya, Sarah E. Smith, Michael Epp, Seth Malloy, Fang Liu, Mark Hembree, Qinghui Mu, Jeffrey S. Haug, Ermanno Malagola, Huzaifa Hassan, Kaitlyn Petentler, Rhonda Egidy, Lucinda Maddera, Linheng Li","doi":"10.1016/j.devcel.2024.10.021","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.021","url":null,"abstract":"The homeostasis of the intestinal epithelium relies on intricate yet insufficiently understood mechanisms of intestinal epithelial plasticity. Here, we elucidate the pivotal role of Frizzled5 (Fzd5), a Wnt pathway receptor, as a determinant of murine intestinal epithelial cell fate. Deletion of Fzd5 in Lgr5<sup>+</sup> intestinal stem cells (ISCs) impairs their self-renewal, whereas its deletion in Krt19<sup>+</sup> cells disrupts lineage generation, without affecting crypt integrity in either case. However, a broader deletion of Fzd5 across the epithelium leads to substantial crypt deterioration. Integrated analysis of single-cell RNA sequencing (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) identifies that Fzd5 governs chromatin accessibility, orchestrating the regulation of stem- and lineage-related gene expression mainly in ISCs and progenitor cells. In summary, our findings provide insights into the regulatory role of Fzd5 in governing intestinal epithelial plasticity.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"254 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ergosterols are essential components of fungal plasma membranes. Inhibitors targeting ergosterol biosynthesis (ERG) genes are critical for controlling fungal pathogens, including Magnaporthe oryzae, the fungus that causes rice blast. However, the translational mechanisms governing ERG gene expression remain largely unexplored. Here, we show that the Trm6/Trm61 complex catalyzes dynamic N1-methyladenosine at position 58 (m1A58) in 51 transfer RNAs (tRNAs) of M. oryzae, significantly influencing translation at both the initiation and elongation stages. Notably, tRNA m1A58 promotes elongation speed at most cognate codons mainly by enhancing eEF1-tRNA binding rather than affecting tRNA abundance or charging. The absence of m1A58 leads to substantial decreases in the translation of ERG genes, ergosterol production, and, consequently, fungal virulence. Simultaneously targeting the Trm6/Trm61 complex and the ergosterol biosynthesis pathway markedly improves rice blast control. Our findings demonstrate an important role of m1A58-mediated translational regulation in ergosterol production and fungal infection, offering a potential strategy for fungicide development.
{"title":"tRNA-m<sup>1</sup>A methylation controls the infection of Magnaporthe oryzae by supporting ergosterol biosynthesis.","authors":"Rongrong He, Ziwei Lv, Yinan Li, Shuchao Ren, Jiaqi Cao, Jun Zhu, Xinrong Zhang, Huimin Wu, Lihao Wan, Ji Tang, Shutong Xu, Xiao-Lin Chen, Zhipeng Zhou","doi":"10.1016/j.devcel.2024.08.002","DOIUrl":"10.1016/j.devcel.2024.08.002","url":null,"abstract":"<p><p>Ergosterols are essential components of fungal plasma membranes. Inhibitors targeting ergosterol biosynthesis (ERG) genes are critical for controlling fungal pathogens, including Magnaporthe oryzae, the fungus that causes rice blast. However, the translational mechanisms governing ERG gene expression remain largely unexplored. Here, we show that the Trm6/Trm61 complex catalyzes dynamic N<sup>1</sup>-methyladenosine at position 58 (m<sup>1</sup>A58) in 51 transfer RNAs (tRNAs) of M. oryzae, significantly influencing translation at both the initiation and elongation stages. Notably, tRNA m<sup>1</sup>A58 promotes elongation speed at most cognate codons mainly by enhancing eEF1-tRNA binding rather than affecting tRNA abundance or charging. The absence of m<sup>1</sup>A58 leads to substantial decreases in the translation of ERG genes, ergosterol production, and, consequently, fungal virulence. Simultaneously targeting the Trm6/Trm61 complex and the ergosterol biosynthesis pathway markedly improves rice blast control. Our findings demonstrate an important role of m<sup>1</sup>A58-mediated translational regulation in ergosterol production and fungal infection, offering a potential strategy for fungicide development.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":"2931-2946.e7"},"PeriodicalIF":10.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18Epub Date: 2024-08-26DOI: 10.1016/j.devcel.2024.08.001
Mariana Romeiro Motta, François Nédélec, Helen Saville, Elke Woelken, Claire Jacquerie, Martine Pastuglia, Sara Christina Stolze, Eveline Van De Slijke, Lev Böttger, Katia Belcram, Hirofumi Nakagami, Geert De Jaeger, David Bouchez, Arp Schnittger
To ensure an even segregation of chromosomes during somatic cell division, eukaryotes rely on mitotic spindles. Here, we measured prime characteristics of the Arabidopsis mitotic spindle and built a three-dimensional dynamic model using Cytosim. We identified the cell-cycle regulator CYCLIN-DEPENDENT KINASE B1 (CDKB1) together with its cyclin partner CYCB3;1 as key regulators of spindle morphology in Arabidopsis. We found that the augmin component ENDOSPERM DEFECTIVE1 (EDE1) is a substrate of the CDKB1;1-CYCB3;1 complex. A non-phosphorylatable mutant rescue of ede1 resembled the spindle phenotypes of cycb3;1 and cdkb1 mutants and the protein associated less efficiently with spindle microtubules. Accordingly, reducing the level of augmin in simulations recapitulated the phenotypes observed in the mutants. Our findings emphasize the importance of cell-cycle-dependent phospho-control of the mitotic spindle in plant cells and support the validity of our model as a framework for the exploration of mechanisms controlling the organization of the eukaryotic spindle.
{"title":"The cell cycle controls spindle architecture in Arabidopsis by activating the augmin pathway.","authors":"Mariana Romeiro Motta, François Nédélec, Helen Saville, Elke Woelken, Claire Jacquerie, Martine Pastuglia, Sara Christina Stolze, Eveline Van De Slijke, Lev Böttger, Katia Belcram, Hirofumi Nakagami, Geert De Jaeger, David Bouchez, Arp Schnittger","doi":"10.1016/j.devcel.2024.08.001","DOIUrl":"10.1016/j.devcel.2024.08.001","url":null,"abstract":"<p><p>To ensure an even segregation of chromosomes during somatic cell division, eukaryotes rely on mitotic spindles. Here, we measured prime characteristics of the Arabidopsis mitotic spindle and built a three-dimensional dynamic model using Cytosim. We identified the cell-cycle regulator CYCLIN-DEPENDENT KINASE B1 (CDKB1) together with its cyclin partner CYCB3;1 as key regulators of spindle morphology in Arabidopsis. We found that the augmin component ENDOSPERM DEFECTIVE1 (EDE1) is a substrate of the CDKB1;1-CYCB3;1 complex. A non-phosphorylatable mutant rescue of ede1 resembled the spindle phenotypes of cycb3;1 and cdkb1 mutants and the protein associated less efficiently with spindle microtubules. Accordingly, reducing the level of augmin in simulations recapitulated the phenotypes observed in the mutants. Our findings emphasize the importance of cell-cycle-dependent phospho-control of the mitotic spindle in plant cells and support the validity of our model as a framework for the exploration of mechanisms controlling the organization of the eukaryotic spindle.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":"2947-2961.e9"},"PeriodicalIF":10.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1016/j.devcel.2024.10.018
Hao Wu, Lanrui Cao, Xinpeng Wen, Jiawei Fan, Yuan Wang, Heyong Hu, Shuyan Ji, Yinli Zhang, Cunqi Ye, Wei Xie, Jin Zhang, Haoxing Xu, Xudong Fu
During mouse preimplantation development, a subset of retrotransposons/genes are transiently expressed in the totipotent 2-cell (2C) embryos. These 2C transcripts rapidly shut down their expression beyond the 2C stage of embryos, promoting the embryo to exit from the 2C stage. However, the mechanisms regulating this shutdown remain unclear. Here, we identified that lysosomal catabolism played a role in the exit of the totipotent 2C state. Our results showed that the activation of embryonic lysosomal catabolism promoted the embryo to exit from the 2C stage and suppressed 2C transcript expression. Mechanistically, our results indicated that lysosomal catabolism suppressed 2C transcripts through replenishing cellular amino-acid levels, thereby inactivating transcriptional factors TFE3/TFEB and abolishing their transcriptional activation of 2C retrotransposons, MERVL (murine endogenous retrovirus-L)/MT2_Mm. Collectively, our study identified that lysosomal activity modulated the transcriptomic landscape and development in mouse embryos and identified an unanticipated layer of transcriptional control on early-embryonic retrotransposons from lysosomal signaling.
{"title":"Lysosomal catabolic activity promotes the exit of murine totipotent 2-cell state by silencing early-embryonic retrotransposons","authors":"Hao Wu, Lanrui Cao, Xinpeng Wen, Jiawei Fan, Yuan Wang, Heyong Hu, Shuyan Ji, Yinli Zhang, Cunqi Ye, Wei Xie, Jin Zhang, Haoxing Xu, Xudong Fu","doi":"10.1016/j.devcel.2024.10.018","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.018","url":null,"abstract":"During mouse preimplantation development, a subset of retrotransposons/genes are transiently expressed in the totipotent 2-cell (2C) embryos. These 2C transcripts rapidly shut down their expression beyond the 2C stage of embryos, promoting the embryo to exit from the 2C stage. However, the mechanisms regulating this shutdown remain unclear. Here, we identified that lysosomal catabolism played a role in the exit of the totipotent 2C state. Our results showed that the activation of embryonic lysosomal catabolism promoted the embryo to exit from the 2C stage and suppressed 2C transcript expression. Mechanistically, our results indicated that lysosomal catabolism suppressed 2C transcripts through replenishing cellular amino-acid levels, thereby inactivating transcriptional factors TFE3/TFEB and abolishing their transcriptional activation of 2C retrotransposons, MERVL (murine endogenous retrovirus-L)/MT2_Mm. Collectively, our study identified that lysosomal activity modulated the transcriptomic landscape and development in mouse embryos and identified an unanticipated layer of transcriptional control on early-embryonic retrotransposons from lysosomal signaling.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"34 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1016/j.devcel.2024.10.012
Michael Housset, Dominic Filion, Nelson Cortes, Hojatollah Vali, Craig A. Mandato, Christian Casanova, Michel Cayouette
The coordinated spatial arrangement of organelles within a tissue plane, known as planar cell polarity (PCP), is critical for organ development and function. Gradients of morphogens and their receptors typically set-up PCP, but whether non-molecular cues, akin to phototropism in plants, also play a part remains unknown. Here, we report that basal bodies of newborn photoreceptor cells in the mouse retina are positioned centrally on the apical surface but then move laterally during the first postnatal week, generating cell-intrinsic asymmetry in the retinal plane. After 1 week, when the eyes open, basal bodies of cone cilia, but not rods, become coordinated across the plane to face the center of the retina. We further show that light is essential for cone PCP, triggering a cascade in which cone transducin interacts with the G-protein-signaling modulator protein 2 (GPSM2) to establish PCP. This work identifies a non-canonical PCP pathway initiated by light.
细胞器在组织平面内的协调空间排列，即平面细胞极性（PCP），对于器官的发育和功能至关重要。形态诱导体及其受体的梯度通常会设置平面细胞极性，但非分子线索（类似于植物中的向光性）是否也在其中起作用仍是未知数。在这里，我们报告了小鼠视网膜中新生感光细胞的基底体在顶端表面居中定位，但在出生后第一周内向侧方移动，从而在视网膜平面上产生细胞内在不对称。1 周后，当眼睛睁开时，视锥纤毛的基底体（而不是视杆细胞）会协调地穿过视网膜平面，面向视网膜中心。我们进一步发现，光对视锥纤毛虫的协调性至关重要，它触发了一个级联，在这个级联中，视锥转导蛋白与 G 蛋白信号调节蛋白 2（GPSM2）相互作用，从而建立起协调性。这项研究发现了一条由光启动的非经典 PCP 通路。
{"title":"Identification of a non-canonical planar cell polarity pathway triggered by light in the developing mouse retina","authors":"Michael Housset, Dominic Filion, Nelson Cortes, Hojatollah Vali, Craig A. Mandato, Christian Casanova, Michel Cayouette","doi":"10.1016/j.devcel.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.012","url":null,"abstract":"The coordinated spatial arrangement of organelles within a tissue plane, known as planar cell polarity (PCP), is critical for organ development and function. Gradients of morphogens and their receptors typically set-up PCP, but whether non-molecular cues, akin to phototropism in plants, also play a part remains unknown. Here, we report that basal bodies of newborn photoreceptor cells in the mouse retina are positioned centrally on the apical surface but then move laterally during the first postnatal week, generating cell-intrinsic asymmetry in the retinal plane. After 1 week, when the eyes open, basal bodies of cone cilia, but not rods, become coordinated across the plane to face the center of the retina. We further show that light is essential for cone PCP, triggering a cascade in which cone transducin interacts with the G-protein-signaling modulator protein 2 (GPSM2) to establish PCP. This work identifies a non-canonical PCP pathway initiated by light.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"99 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1016/j.devcel.2024.10.020
A. Sophie Brumm, Afshan McCarthy, Claudia Gerri, Todd Fallesen, Laura Woods, Riley McMahon, Athanasios Papathanasiou, Kay Elder, Phil Snell, Leila Christie, Patricia Garcia, Valerie Shaikly, Mohamed Taranissi, Paul Serhal, Rabi A. Odia, Mina Vasilic, Anna Osnato, Peter J. Rugg-Gunn, Ludovic Vallier, Caroline S. Hill, Kathy K. Niakan
The human blastocyst contains the pluripotent epiblast from which human embryonic stem cells (hESCs) can be derived. ACTIVIN/NODAL signaling maintains expression of the transcription factor NANOG and in vitro propagation of hESCs. It is unknown whether this reflects a functional requirement for epiblast development in human embryos. Here, we characterized NODAL signaling activity during pre-implantation human development. We showed that NANOG is an early molecular marker restricted to the nascent human pluripotent epiblast and was initiated prior to the onset of NODAL signaling. We further demonstrated that expression of pluripotency-associated transcription factors NANOG, SOX2, OCT4, and KLF17 were maintained in the epiblast in the absence of NODAL signaling activity. Genome-wide transcriptional analysis showed that NODAL signaling inhibition did not decrease NANOG transcription or impact the wider pluripotency-associated gene regulatory network. These data suggest differences in the signaling requirements regulating pluripotency in the pre-implantation human epiblast compared with existing hESC culture.
{"title":"Initiation and maintenance of the pluripotent epiblast in pre-implantation human development is independent of NODAL signaling","authors":"A. Sophie Brumm, Afshan McCarthy, Claudia Gerri, Todd Fallesen, Laura Woods, Riley McMahon, Athanasios Papathanasiou, Kay Elder, Phil Snell, Leila Christie, Patricia Garcia, Valerie Shaikly, Mohamed Taranissi, Paul Serhal, Rabi A. Odia, Mina Vasilic, Anna Osnato, Peter J. Rugg-Gunn, Ludovic Vallier, Caroline S. Hill, Kathy K. Niakan","doi":"10.1016/j.devcel.2024.10.020","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.020","url":null,"abstract":"The human blastocyst contains the pluripotent epiblast from which human embryonic stem cells (hESCs) can be derived. ACTIVIN/NODAL signaling maintains expression of the transcription factor <em>NANOG</em> and <em>in vitro</em> propagation of hESCs. It is unknown whether this reflects a functional requirement for epiblast development in human embryos. Here, we characterized NODAL signaling activity during pre-implantation human development. We showed that NANOG is an early molecular marker restricted to the nascent human pluripotent epiblast and was initiated prior to the onset of NODAL signaling. We further demonstrated that expression of pluripotency-associated transcription factors NANOG, SOX2, OCT4, and KLF17 were maintained in the epiblast in the absence of NODAL signaling activity. Genome-wide transcriptional analysis showed that NODAL signaling inhibition did not decrease <em>NANOG</em> transcription or impact the wider pluripotency-associated gene regulatory network. These data suggest differences in the signaling requirements regulating pluripotency in the pre-implantation human epiblast compared with existing hESC culture.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"76 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.devcel.2024.10.019
Yannick Carrier, Laura Quintana Rio, Nadia Formicola, Vicente de Sousa-Xavier, Maha Tabet, Yu-Chieh David Chen, Aicha Haji Ali, Maëva Wislez, Lisa Orts, Alexander Borst, Filipe Pinto-Teixeira
Layer-specific brain computations depend on neurons synapsing with specific partners in distinct laminae. In the Drosophila lobula plate, axons of the four subtypes of T4 and T5 visual motion direction-selective neurons segregate into four layers, where they synapse with distinct subsets of postsynaptic neurons. Here, we identify a layer-specific expression of different receptor-ligand pairs of the Beat and Side families of cell adhesion molecules between T4/T5s and their postsynaptic partners. Developmental genetic analysis demonstrate that Beat/Side-mediated interactions are required to restrict innervation of T4/T5 axons and the dendrites of their partners to a single layer. We show that Beat/Side interactions are not required for synaptogenesis. Instead, they contribute to synaptic specificity by biasing cellular adjacency, causing neurons to segregate in discrete layers, restricting partner availability before synaptogenesis. We propose that the emergence of synaptic specificity relies on a competitive dynamic among postsynaptic partners with shared Beat/Side expression to adhere with T4/T5s.
{"title":"Biased cell adhesion organizes the Drosophila visual motion integration circuit","authors":"Yannick Carrier, Laura Quintana Rio, Nadia Formicola, Vicente de Sousa-Xavier, Maha Tabet, Yu-Chieh David Chen, Aicha Haji Ali, Maëva Wislez, Lisa Orts, Alexander Borst, Filipe Pinto-Teixeira","doi":"10.1016/j.devcel.2024.10.019","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.019","url":null,"abstract":"Layer-specific brain computations depend on neurons synapsing with specific partners in distinct laminae. In the <em>Drosophila</em> lobula plate, axons of the four subtypes of T4 and T5 visual motion direction-selective neurons segregate into four layers, where they synapse with distinct subsets of postsynaptic neurons. Here, we identify a layer-specific expression of different receptor-ligand pairs of the Beat and Side families of cell adhesion molecules between T4/T5s and their postsynaptic partners. Developmental genetic analysis demonstrate that Beat/Side-mediated interactions are required to restrict innervation of T4/T5 axons and the dendrites of their partners to a single layer. We show that Beat/Side interactions are not required for synaptogenesis. Instead, they contribute to synaptic specificity by biasing cellular adjacency, causing neurons to segregate in discrete layers, restricting partner availability before synaptogenesis. We propose that the emergence of synaptic specificity relies on a competitive dynamic among postsynaptic partners with shared Beat/Side expression to adhere with T4/T5s.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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