EMBO Journal最新文献

Structural insights into bacterial dimethylsulfoniopropionate import by BCCT-family transporters. bcct家族转运体对细菌二甲基磺丙酸盐进口的结构研究。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-08 DOI: 10.1038/s44318-026-00798-w

Yu-Zhong Zhang, Wen-Jing Zhu, Kang Li, Hai-Tao Ding, Motoyuki Hattori, Shuaimeng Liu, Chang Ge, Qi-Long Qin, Zhao-Jie Teng, Ning-Hua Liu, Hai-Yan Cao, Chun-Yang Li, Xiu-Lan Chen, Qing-Tao Shen, Jonathan D Todd, Lu-Ning Liu, Peng Wang

{"title":"Structural insights into bacterial dimethylsulfoniopropionate import by BCCT-family transporters.","authors":"Yu-Zhong Zhang, Wen-Jing Zhu, Kang Li, Hai-Tao Ding, Motoyuki Hattori, Shuaimeng Liu, Chang Ge, Qi-Long Qin, Zhao-Jie Teng, Ning-Hua Liu, Hai-Yan Cao, Chun-Yang Li, Xiu-Lan Chen, Qing-Tao Shen, Jonathan D Todd, Lu-Ning Liu, Peng Wang","doi":"10.1038/s44318-026-00798-w","DOIUrl":"https://doi.org/10.1038/s44318-026-00798-w","url":null,"abstract":"Dimethylsulfoniopropionate (DMSP) is a ubiquitous marine organosulfur compound central to microbial stress responses, chemotaxis, and nutrient cycling. Its catabolism produces dimethylsulfide (DMS), a climate-active gas, and plays a key role in the global sulfur cycle. However, the molecular basis of DMSP import, underpinning its microbial metabolism, remains poorly understood. Here, we identify and characterize the BCCT-family transporter DddT from Psychrobacter sp. D2, a marine gamma-proteobacterium that utilizes DMSP as a carbon source. DddT is essential for DMSP uptake and functions as a Na+-coupled symporter driven by the transmembrane sodium gradient. Using cryo-electron microscopy, we determined DddT structures in multiple conformational states, revealing its Na+-dependent transport mechanism involving two sodium ions, one coordinated by a previously uncharacterized binding site. Sequence analysis shows that DddT-like proteins with conserved sodium-binding features are widespread in marine bacteria, suggesting this Na+-coupled transport mechanism represents a broadly conserved feature of the BCCT family. Our findings provide mechanistic insights into sodium-driven substrate uptake and marine sulfur cycling.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857625","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}

引用次数: 0

SLX4IP limits replication stress globally and at ALT telomeres. SLX4IP限制了全球和ALT端粒的复制压力。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-07 DOI: 10.1038/s44318-026-00790-4

Jessica Spindler, Francesca Pandolfo, Anna Eva Koch, Priscilla Piccirillo, Drew Jordahl, Nikhil Venkatesh, Dhruthi Suresh, K R Ylvisaker, Anita Jopkiewicz, Johanna Bihler, Sandra Buschbaum, Marcel Morgenstern, Katherine A Overmyer, Estelle Vincendeau, Joshua J Coon, Pei-Chi Wei, Robert Hänsel-Hertsch, Kavi P M Mehta, Stephanie Panier

{"title":"SLX4IP limits replication stress globally and at ALT telomeres.","authors":"Jessica Spindler, Francesca Pandolfo, Anna Eva Koch, Priscilla Piccirillo, Drew Jordahl, Nikhil Venkatesh, Dhruthi Suresh, K R Ylvisaker, Anita Jopkiewicz, Johanna Bihler, Sandra Buschbaum, Marcel Morgenstern, Katherine A Overmyer, Estelle Vincendeau, Joshua J Coon, Pei-Chi Wei, Robert Hänsel-Hertsch, Kavi P M Mehta, Stephanie Panier","doi":"10.1038/s44318-026-00790-4","DOIUrl":"https://doi.org/10.1038/s44318-026-00790-4","url":null,"abstract":"Faithful DNA replication is essential for genome stability, yet replication forks face constant stress. The Bloom syndrome helicase (BLM) safeguards fork integrity, but excessive BLM activity can itself induce replication stress. We identify SLX4IP as a genome-wide regulator that restrains BLM to maintain replication fork stability. SLX4IP localizes broadly across chromatin with recruitment enhanced under replication stress. Loss of SLX4IP slows replication forks, remodels the replisome, and generates post-replicative single-stranded DNA gaps that are accompanied by elevated nuclear ADP ribose, reflecting compromised replication integrity. These defects are driven by dysregulated BLM activity, establishing SLX4IP as a negative regulator of BLM-dependent replication stress. At ALT telomeres, SLX4IP deficiency triggers ATR signaling, telomere fragility, and accumulation of ALT-associated PML bodies. Here, SLX4IP functions in parallel with FANCM to restrain BLM at ALT telomeres, with co-depletion of SLX4IP and FANCM causing synthetic lethality in ALT-positive cells, a phenotype fully rescued by BLM loss. Together, our results define SLX4IP as a critical genome-wide regulator of replication fork integrity and reveal SLX4IP as a potential vulnerability in ALT-positive cancers.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845595","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}

引用次数: 0

Cytosolic DNA inhibits rDNA transcription by retaining the RNA polymerase I transcription machinery. 胞质DNA通过保留RNA聚合酶I转录机制抑制rDNA转录。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-05 DOI: 10.1038/s44318-026-00792-2

Yinfeng Xu, Qian Wang, Chuying Qian, Sheng Lu, Zhengfu He, Wei Liu, Wei Wan

{"title":"Cytosolic DNA inhibits rDNA transcription by retaining the RNA polymerase I transcription machinery.","authors":"Yinfeng Xu, Qian Wang, Chuying Qian, Sheng Lu, Zhengfu He, Wei Liu, Wei Wan","doi":"10.1038/s44318-026-00792-2","DOIUrl":"https://doi.org/10.1038/s44318-026-00792-2","url":null,"abstract":"Cytosolic DNA, derived from cellular damage or microbial infection, functions as a pivotal trigger for the host innate immune responses by activating intracellular DNA-sensing machinery, including the cGAS-STING pathway. However, whether cytosolic DNA is involved in DNA-sensing pathway-independent biological processes remains largely unknown. Here, we show that cytosolic DNA interacts with UBTF and POLR1A, two essential components of the RNA polymerase I transcription machinery, and sequesters these two proteins in the cytoplasm. This retention decreases nuclear UBTF and POLR1A, inhibits rDNA transcription, suppresses protein synthesis, and curtails cell proliferation. Furthermore, we demonstrate that STING-induced autophagy specifically eliminates cytosolic DNA and restores nuclear UBTF and POLR1A, thereby abolishing the inhibitory effects of cytosolic DNA on rDNA transcription, protein synthesis, and cell proliferation. Thus, our findings uncover a novel role of cytosolic DNA in rDNA transcription, suggesting that cytosolic DNA not only activates immune responses but also interferes with cell metabolism.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845644","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}

引用次数: 0

Phosphorylation tunes p62 condensates to drive autophagic degradation of ubiquitinated proteins. 磷酸化调节p62凝聚物来驱动泛素化蛋白的自噬降解。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-05 DOI: 10.1038/s44318-026-00785-1

Satoko Komatsu-Hirota, Keisuke Tabata, Yu-Shin Sou, Soichiro Kakuta, Jun-Ichi Sakamaki, Hikaru Tsuchiya, Jiachen Li, Hiroyuki Kumeta, Yuji Sakai, Yuko Fujioka, Daisuke Noshiro, Shunsuke F Shimobayashi, Tomo Kurimura, Takashi Taniguchi, Manabu Abe, Masato Koike, Hideaki Morishita, Nobuo N Noda, Masaaki Komatsu

{"title":"Phosphorylation tunes p62 condensates to drive autophagic degradation of ubiquitinated proteins.","authors":"Satoko Komatsu-Hirota, Keisuke Tabata, Yu-Shin Sou, Soichiro Kakuta, Jun-Ichi Sakamaki, Hikaru Tsuchiya, Jiachen Li, Hiroyuki Kumeta, Yuji Sakai, Yuko Fujioka, Daisuke Noshiro, Shunsuke F Shimobayashi, Tomo Kurimura, Takashi Taniguchi, Manabu Abe, Masato Koike, Hideaki Morishita, Nobuo N Noda, Masaaki Komatsu","doi":"10.1038/s44318-026-00785-1","DOIUrl":"https://doi.org/10.1038/s44318-026-00785-1","url":null,"abstract":"p62/SQSTM1 self-assembles with polyubiquitin into liquid-like condensates (\"p62 bodies\") that function as stress-signaling hubs and selective autophagy cargo. We show that TBK1-dependent phosphorylation at Ser403 acts as a threshold-dependent modulator of a condensate's physical properties and promotes their rapid autophagic clearance. Phosphorylation within p62 bodies drives a transition from large, fluid droplets to compact, gel-like condensates that efficiently capture LC3-positive isolation membranes and accelerate the autophagic removal of ubiquitinated proteins. PP2A holoenzymes containing PPP2R5A/B/E, recruited via a KEAP1 bridge, counteract TBK1 by dephosphorylating Ser403. Homozygous p62S403E/S403E knock-in embryonic stem cells differentiate into post-mitotic neurons enriched in miniaturized, gel-like p62 bodies. Consistently, phosphorylation-mimetic knock-in mice show similar remodeling of p62 condensates in vivo, demonstrating that this phosphorylation-driven mechanism maintains proteostasis across scales. We propose that Ser403 phosphorylation functions as a molecular switch that couples the material state of p62 condensates to their stability and serves as a central control point for p62-mediated protein degradation.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845564","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}

引用次数: 0

Structures of the neutral amino acid transporter LAT4 provide insights into antitumor effects of its inhibitor tubeimoside-1. 中性氨基酸转运体LAT4的结构为其抑制剂tubeimoside-1的抗肿瘤作用提供了新的见解。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-04 DOI: 10.1038/s44318-026-00786-0

Dian Ding, Yishuo Lu, Jingyi Yang, Hongyi Chen, Peijun Jiang, Yan Jin, Jianyuan Luo, Guangxi Wang, Yuxin Yin

{"title":"Structures of the neutral amino acid transporter LAT4 provide insights into antitumor effects of its inhibitor tubeimoside-1.","authors":"Dian Ding, Yishuo Lu, Jingyi Yang, Hongyi Chen, Peijun Jiang, Yan Jin, Jianyuan Luo, Guangxi Wang, Yuxin Yin","doi":"10.1038/s44318-026-00786-0","DOIUrl":"https://doi.org/10.1038/s44318-026-00786-0","url":null,"abstract":"Methionine restriction has emerged as a promising strategy for extending lifespan and enhancing cancer therapy. LAT4, an amino acid transporter encoded by SLC43A2, is frequently overexpressed in multiple cancers and critically contributes to systemic methionine accumulation. However, the structural basis of LAT4 function remains poorly understood, and no effective inhibitors have been developed to date. In this study, we present high-resolution cryo-electron microscopy structures of LAT4 and the related SLC43A3-encoded purine transporter ENBT1. The phenylalanine-bound structure of LAT4 enables the characterization of the substrate binding pocket. Comparison of the outward-facing ENBT1 and inward-facing LAT4 structures identifies key residues involved in the methionine transport process. Structural analysis of digitonin binding to the central cavity of LAT4 enabled identification of tubeimoside-1 (TBM-1) as a potent inhibitor of LAT4-mediated methionine uptake. We demonstrate that tubeimoside-1 reduces methionine uptake in B16F10 cancer cells. Furthermore, TBM-1 suppresses tumor progression in the MMTV-PyVT mouse model of breast cancer through systemic methionine restriction. Our study provides insights into the LAT4 transport mechanism and identifies tubeimoside-1 as a potent inhibitor of methionine uptake and establishes a foundation for developing LAT4-targeting therapeutics to restrict methionine uptake.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845575","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}

引用次数: 0

Peroxisome-derived ether lipids regulate lysosomal exocytosis. 过氧化物酶体衍生的醚脂调节溶酶体胞吐。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-02 DOI: 10.1038/s44318-026-00791-3

Liang Chen, Danielle Henn, Zhongzheng Dong, Jiaxuan Liang, Aleksander Wielenga, Goncalo Vale, Bala Burugula, Junyi Zou, Yamuna Krishnan, Jeffrey G McDonald, Jacob Kitzman, Ming Li

{"title":"Peroxisome-derived ether lipids regulate lysosomal exocytosis.","authors":"Liang Chen, Danielle Henn, Zhongzheng Dong, Jiaxuan Liang, Aleksander Wielenga, Goncalo Vale, Bala Burugula, Junyi Zou, Yamuna Krishnan, Jeffrey G McDonald, Jacob Kitzman, Ming Li","doi":"10.1038/s44318-026-00791-3","DOIUrl":"10.1038/s44318-026-00791-3","url":null,"abstract":"Lysosomes and peroxisomes are essential for cellular homeostasis, yet how their activities are coordinated remains poorly understood. Here, we identify peroxisome-derived ether lipids as key regulators of lysosomal function. A genome-wide CRISPR/Cas9 screen in LYSET-deficient mucolipidosis V cells revealed that disruption of ether lipid synthesis genes or peroxins markedly reduces lysosome accumulation and restores degradative capacity. Genetic or pharmacological inhibition of ether lipid synthesis enhanced lysosomal exocytosis and promoted the clearance of undigested material independently of mannose-6-phosphate trafficking. Conversely, supplementation with the ether lipid precursor hexadecylglycerol increased lysosome abundance, while reducing their degradative capacity. These findings uncover a peroxisome-lysosome metabolic axis, in which ether lipids act as bidirectional regulators of lysosomal number and function independently of the lysosomal master regulator TFEB. Our findings reveal how peroxisome-localized lipid metabolism modulates lysosomal homeostasis, and suggest potential new strategies to combat lysosomal and peroxisomal disorders.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822117","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}

引用次数: 0

Spatial metabolomics: design, pitfalls and data interpretation. 空间代谢组学：设计、陷阱和数据解释。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-02 DOI: 10.1038/s44318-026-00797-x

Prasad Phapale

引用次数: 0

Retrovirus insertions in host transcripts trigger de novo piRNA immunity. 逆转录病毒插入宿主转录本触发piRNA从头免疫。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-02 DOI: 10.1038/s44318-026-00777-1

Baptiste Rafanel, Liudmila Protsenko, Dominik Handler, Julius Brennecke, Kirsten-André Senti

{"title":"Retrovirus insertions in host transcripts trigger de novo piRNA immunity.","authors":"Baptiste Rafanel, Liudmila Protsenko, Dominik Handler, Julius Brennecke, Kirsten-André Senti","doi":"10.1038/s44318-026-00777-1","DOIUrl":"https://doi.org/10.1038/s44318-026-00777-1","url":null,"abstract":"How host organisms adapt their defense systems to newly invading transposable elements remains poorly understood. Here, we show how Drosophila melanogaster acquired PIWI-interacting RNA (piRNA)-mediated immunity against the endogenous retrovirus Tirant. We uncover two distinct modes of de novo piRNA biogenesis by combining genetics, small RNA profiling, and population genomics. The primary route involves antisense insertions into the flamenco cluster, a master locus for transposon control. Unexpectedly, a second, equally potent mechanism arises from antisense Tirant insertions within host gene 3' UTRs. This process requires host gene transcription but is independent of host gene identity. Our findings challenge prevailing models that tie piRNA precursor specification to genomic origin or nuclear RNA processing context. Instead, they reveal a flexible mechanism that turns a critical vulnerability of transposons into an advantage for the host. When transposition occurs into host gene exons, chimeric antisense transcripts are exported to the cytoplasm, inadvertently initiating piRNA production and enabling rapid, adaptive genome defense against new invaders.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822376","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}

引用次数: 0

Antibiotic-induced gut microbiome dysbiosis: risks and strategies for mitigation. 抗生素引起的肠道微生物群失调：风险和缓解策略。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-02 DOI: 10.1038/s44318-026-00796-y

Katharina Müller, Justine Gillard, Athanasios Typas, Michael Knopp, Camille V Goemans

{"title":"Antibiotic-induced gut microbiome dysbiosis: risks and strategies for mitigation.","authors":"Katharina Müller, Justine Gillard, Athanasios Typas, Michael Knopp, Camille V Goemans","doi":"10.1038/s44318-026-00796-y","DOIUrl":"https://doi.org/10.1038/s44318-026-00796-y","url":null,"abstract":"The discovery of antibiotics and their subsequent therapeutic use revolutionized our ability to treat once deadly infectious diseases, and antibiotics have become one of the most commonly prescribed drug classes. Unfortunately, these compounds not only target pathogenic strains, but also non-pathogenic bacteria that fulfill important functions for the human host. As such, antibiotic treatment can cause severe collateral damage, resulting in dysbiosis, for example, in the human gut microbiome. Given the immense importance of the gut microbiome for human health, antibiotic-induced dysbiosis can cause a variety of detrimental health outcomes. In addition, antibiotic (over-)use causes selection of antibiotic-resistant strains, and the human gut microbiome has become a major reservoir for resistance determinants that can transfer to pathogenic isolates and cause hard-to-treat infections. In this review, we describe various adverse effects that antibiotic use has on the human gut microbiome, how we can approach this problem experimentally, and discuss pathways to mitigate antibiotic-induced collateral damage.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823175","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}

引用次数: 0

Novel tissue mechanics-guided cellular flows drive the formation of feather follicles. 新的组织力学引导的细胞流动驱动羽毛毛囊的形成。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-02 DOI: 10.1038/s44318-026-00771-7

Hans I-Chen Harn, Ting-Xin Jiang, Chih-Han Huang, Wen-Tau Juan, Tzu-Yu Liu, Tsao-Chi Chuang, Wan-Chi Liao, Yingxiao Wang, Ji Li, Cornelis J Weijer, Ping Wu, Chin-Lin Guo, Cheng-Ming Chuong

{"title":"Novel tissue mechanics-guided cellular flows drive the formation of feather follicles.","authors":"Hans I-Chen Harn, Ting-Xin Jiang, Chih-Han Huang, Wen-Tau Juan, Tzu-Yu Liu, Tsao-Chi Chuang, Wan-Chi Liao, Yingxiao Wang, Ji Li, Cornelis J Weijer, Ping Wu, Chin-Lin Guo, Cheng-Ming Chuong","doi":"10.1038/s44318-026-00771-7","DOIUrl":"10.1038/s44318-026-00771-7","url":null,"abstract":"Complex tissue architecture is achieved through multiple rounds of morphological transitions. Here, we analyzed cellular flows and tissue mechanics during avian skin development by employing chicken and transgenic quail skin explant models. We demonstrate how novel cellular flows initiate chemo-mechanical circuits that guide epithelial protrusion, folding, invagination, and spatial cell fate specification. During initial feather bud formation, stiff dermal condensates protrude vertically from the locally softened epithelial sheet. As the bud elongates, it stretches the epithelial cells at the base, thus mechanically activating YAP, which causes the epithelial sheet to fold downward and form a stiff cylindrical wall that invaginates into the skin. This stiff epithelial tongue is essential for the compaction and formation of the tightly packed dermal papillae. These topological transformational events are mechanically interconnected, and the completion of one circuit initiates the next. In contrast, during scale development, the rigid epithelial sheet restricts dermal cell flows, preventing further topological transformation. Based on these findings, we developed a topological transformation model describing how this process enabled the evolution of feather follicles from scales.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822209","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}

引用次数: 0