{"title":"Transcriptional conservation and evolutionary divergence of cell types across mammalian hypothalamus development","authors":"Zhen-Hua Chen, Taotao Bruce Pan, Yu-Hong Zhang, Ben Wang, Xue-Lian Sun, Meixi Gao, Yang Sun, Mingrui Xu, Shuhui Han, Xiang Shi, Felipe Correa-da-Silva, Chenlu Yang, Junfu Guo, Haoda Wu, Yu Zheng Li, Xiu-Qin Liu, Fei Gao, Zhiheng Xu, Shengjin Xu, Xin Liu, Qing-Feng Wu","doi":"10.1016/j.devcel.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.009","url":null,"abstract":"The hypothalamus, an “ancient” subcortical brain structure, maintains physiological homeostasis and controls native behaviors. The evolution of homeostatic regulation and behavioral control in mammals may rely on adaptable neuronal identity establishment but conserved neural patterning mechanisms during neurodevelopment. Here, we combined single-cell, single-nucleus, and spatial transcriptomic datasets to map the spatial patterning of diverse progenitor domains and reconstruct their neurogenic lineages in the developing human and mouse hypothalamus. While the regional organizers orchestrating neural patterning are conserved between primates and rodents, we identified a human-enriched neuronal subtype and found a substantial increase in neuromodulatory gene expression among human neurons. Furthermore, cross-species comparison demonstrated a potential redistribution of two neuroendocrine neuronal subtypes and a shift in inter-transmitter and transmitter-peptide coupling within hypothalamic dopamine neurons. Together, our study lays a critical foundation for understanding cellular development and evolution of the mammalian hypothalamus.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"92 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798387","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}
Developmental cellPub Date : 2025-04-08DOI: 10.1016/j.devcel.2025.03.010
Jennifer Landino, Eileen Misterovich, Lotte van den Goor, Babli Adhikary, Shahana Chumki, Lance A. Davidson, Ann L. Miller
{"title":"Neighbor cells restrain furrowing during Xenopus epithelial cytokinesis","authors":"Jennifer Landino, Eileen Misterovich, Lotte van den Goor, Babli Adhikary, Shahana Chumki, Lance A. Davidson, Ann L. Miller","doi":"10.1016/j.devcel.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.010","url":null,"abstract":"Cytokinesis challenges epithelial tissue homeostasis by generating forces that pull on neighboring cells. Junction reinforcement at the furrow in <em>Xenopus</em> epithelia regulates the speed of furrowing, suggesting that cytokinesis is subject to resistive forces from epithelial neighbors. We show that contractility factors accumulate near the furrow in neighboring cells, and increasing neighbor cell stiffness slows furrowing. Optogenetically increasing contractility in one or both neighbor cells slows furrowing or induces cytokinetic failure. Uncoupling mechanotransduction between dividing cells and their neighbors increases the furrow ingression rate, alters topological cell packing following cytokinesis, and impairs barrier function at the furrow. Computational modeling validates our findings and provides additional insights about epithelial mechanics during cytokinesis. We conclude that forces from the cytokinetic array must be carefully balanced with restraining forces generated by neighbor cells to regulate the speed and success of cytokinesis and maintain epithelial homeostasis.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"38 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798389","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}
Developmental cellPub Date : 2025-04-07DOI: 10.1016/j.devcel.2025.03.006
Michalis Gounis, Hellyeh Hamidi, Johanna Ivaska
{"title":"mTORC1 shutdown unleashes TFEB to drive triple-negative breast cancer invasion","authors":"Michalis Gounis, Hellyeh Hamidi, Johanna Ivaska","doi":"10.1016/j.devcel.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.006","url":null,"abstract":"The PI3K/AKT/mTOR pathway is considered a key therapeutic target in triple-negative breast cancer (TNBC). In this issue of <em>Developmental Cell</em>, Remy et al. challenge this idea by demonstrating that mTORC1 inhibition activates TFEB, promoting MT1-MMP exocytosis, ECM degradation, and increased cell invasion, especially when combined with chemotherapy.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"217 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789761","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}
Developmental cellPub Date : 2025-04-07DOI: 10.1016/j.devcel.2025.02.005
Na Zhang, Daichao Xu
{"title":"Controlling pyroptosis through post-translational modifications of gasdermin D","authors":"Na Zhang, Daichao Xu","doi":"10.1016/j.devcel.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.005","url":null,"abstract":"Pyroptosis, a lytic and programmed cell death pathway, is mediated by gasdermins (GSDMs), with GSDMD playing an important role in innate immunity and pathology. Upon activation, GSDMD is cleaved to release the active N-terminal fragment that oligomerizes into membrane pores, which promote pyroptosis and cytokine secretion, leading to inflammation. Emerging evidence indicates that post-translational modification (PTM) is an important regulatory mechanism of GSDMD activity. This review explores how PTMs, aside from proteolytic cleavage, control GSDMD activity and link biological contexts to pyroptosis in innate immunity and inflammation, which could inform future studies and therapeutic solutions for treating inflammatory conditions.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"20 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789763","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}
Developmental cellPub Date : 2025-04-07DOI: 10.1016/j.devcel.2025.02.004
Weaverly Colleen Lee, Scott J. Dixon
{"title":"Mechanisms of ferroptosis sensitization and resistance","authors":"Weaverly Colleen Lee, Scott J. Dixon","doi":"10.1016/j.devcel.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.004","url":null,"abstract":"Ferroptosis is an iron-dependent and oxidative form of non-apoptotic cell death with roles in development, homeostasis, and disease. Ferroptosis sensitivity can vary between cells, often for reasons that are not well understood. In this perspective, we describe the core ferroptosis mechanism and outline how changes in iron, redox, and lipid metabolism can alter ferroptosis sensitivity. We propose the concept of a ferroptosis sensitivity-resistance continuum to describe how different intrinsic and extrinsic factors interact to push cells toward a more ferroptosis-sensitive or ferroptosis-resistant state, with effects on development and diseases such as cancer.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"6 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789762","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}
Developmental cellPub Date : 2025-04-03DOI: 10.1016/j.devcel.2025.03.008
Nai Yang Yeat, Li-Heng Liu, Yu-Hsuan Chang, Charles Pin-Kuang Lai, Ruey-Hwa Chen
{"title":"Bro1 proteins determine tumor immune evasion and metastasis by controlling secretion or degradation of multivesicular bodies","authors":"Nai Yang Yeat, Li-Heng Liu, Yu-Hsuan Chang, Charles Pin-Kuang Lai, Ruey-Hwa Chen","doi":"10.1016/j.devcel.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.008","url":null,"abstract":"Exosomes play pleiotropic tumor-promoting functions and are secreted by fusion of multivesicular bodies (MVBs) with the plasma membrane. However, MVBs are also directed to lysosomes for degradation, and the mechanism controlling different fates of MVBs remains elusive. Here, we show that the pro-tumor protein WDR4 enhances exosome secretion from mouse and human cancer cells through degrading the endosomal sorting complex required for transport (ESCRT)-associated Bro1-family protein PTPN23. Mechanistically, PTPN23 and ALIX compete for binding to syntenin, thereby directing MVBs toward degradation and secretion, respectively. ALIX, but not PTPN23, recruits actin-capping proteins CAPZA1/CAPZB to prevent branched filamentous actin (F-actin) accumulation around MVBs, thus enabling MVBs trafficking to the cell periphery for secretion. Functionally, WDR4/ALIX-dependent exosomes load a set of pro-tumor proteins through LAMP2A, thereby potentiating metastasis and immune evasion in mice. Our study highlights a previously unappreciated coupling between the biogenesis mechanism and the fate decision of MVBs and its importance in determining exosomal cargos, which have a profound impact on tumor progression.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"224 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766837","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}
Developmental cellPub Date : 2025-04-02DOI: 10.1016/j.devcel.2025.03.007
Xiaozhen Huang, Nan Xiao, Yue Xie, Cao Xu
{"title":"ROS burst prolongs transcriptional condensation to slow shoot apical meristem maturation and achieve heat-stress resilience in tomato","authors":"Xiaozhen Huang, Nan Xiao, Yue Xie, Cao Xu","doi":"10.1016/j.devcel.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.007","url":null,"abstract":"The transition of the shoot apical meristem (SAM) from vegetative growth to flowering, a key step of angiosperm reproductive success, is highly vulnerable to heat stress. Overproduction of reactive oxygen species (ROS) is a hallmark of such environmental stresses, but how SAM exploits the extra ROS to achieve heat-stress resilience is largely unknown. Here, we report that tomato plants respond to heat-induced ROS burst by slowing down SAM maturation and lengthening the vegetative state to achieve heat resilience. Heat-induced extra ROS prolonged the transcriptional condensation status of TERMINATING FLOWER (TMF), a prion-like transcription repressor that undergoes phase separation by sensing hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), therefore temporarily delaying activation of flowering transition and extending vegetative growth. Loss-of-function of TMF, or base editing of a single cysteine residue that senses H<sub>2</sub>O<sub>2</sub>, abolishes heat resilience. Our findings demonstrate that transcriptional reprogramming triggered by ROS might be a molecular basis of plant developmental plasticity underlying heat-stress resilience.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"104 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758394","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}
{"title":"KIF2C promotes paclitaxel resistance by depolymerizing polyglutamylated microtubules","authors":"Yuan-Shao Pao, Kuan-Ju Liao, Ya-Chia Shiau, Ming-Hong Chao, Mu-Chun Li, Li-Mei Lin, Hsin-Huei Chang, Hung-Wei Yeh, Yi-Ju Chen, Yu-Ting Chiu, Max Yu-Chen Pan, Yu-Hsuan Chang, Shih-Yu Shen, Shu-Yu Lin, Hui-Chun Cheng, Yu-Chun Lin, Yuh-Ju Sun, Ching-Chuan Kuo, Hsing-Pang Hsieh, Lily Hui-Ching Wang","doi":"10.1016/j.devcel.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.004","url":null,"abstract":"The long-term effectiveness of paclitaxel is limited by chemoresistance. In this study, we elucidate the molecular mechanism by which kinesin family member 2C (KIF2C), a well-known microtubule depolymerase, contributes to the development of chemoresistance in triple-negative breast cancer (TNBC). We observed elevated levels of KIF2C, tubulin tyrosination, and polyglutamylation in human and mouse breast cancer cells resistant to paclitaxel. Additionally, these chemoresistant cells possessed cross-resistance to diverse microtubule-targeting agents (MTAs). We demonstrated that KIF2C preferentially depolymerizes polyglutamylated tubulin, even in the presence of paclitaxel. To counter this, we developed 7S9, a chemical inhibitor of KIF2C, that prohibits the dissociation of KIF2C from microtubules. The combination of 7S9 and paclitaxel significantly reduced tumorigenesis in chemoresistant TNBC model in mice. Moreover, 7S9 diminished cancer cell chemoresistance to several clinically available MTAs. Our findings elucidate the molecular mechanism of KIF2C-mediated chemoresistance and highlight KIF2C as a promising target for combating cross-resistance in TNBC.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"7 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723809","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}
Developmental cellPub Date : 2025-03-28DOI: 10.1016/j.devcel.2025.03.005
Zachary J. Wright, Nathan E. Tharp, Bonnie Bartel
{"title":"ER nests are specialized ER subdomains in Arabidopsis where peroxisomes and lipid droplets form","authors":"Zachary J. Wright, Nathan E. Tharp, Bonnie Bartel","doi":"10.1016/j.devcel.2025.03.005","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.005","url":null,"abstract":"Organelles are defining features of eukaryotic cells, yet much remains to be learned about organelle biogenesis. Lipid droplets and peroxisomes, which play opposing roles in storing and catabolizing fats, form from a mysterious domain in the endoplasmic reticulum (ER). We used live-cell fluorescence microscopy to visualize peroxisome and lipid droplet biogenesis in young Arabidopsis seedlings, where lipid catabolism is active, and peroxisomes can be unusually large. We found that the ER domains where these organelles are born, which we term ER nests, are complex, dynamic structures that exclude general ER proteins but accumulate other proteins, including lipid biosynthetic enzymes and the COPII component SAR1. Furthermore, ER nests appear to define peroxisome-lipid droplet contact sites. Our findings provide a framework for understanding how these domains form and sort their protein components, illuminate eukaryotic lipid biosynthesis, and elucidate how distinct organelles arise from the ER.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"183 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723810","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}
Developmental cellPub Date : 2025-03-26DOI: 10.1016/j.devcel.2025.03.001
Rory Osborne, Anne-Marie Labandera, Alex J. Ryder, Anastasia Kanali, Tianyuan Xu, Oluwatunmise Akintewe, Maximillian A. Schwarze, Christian D. Morgan, Sjon Hartman, Eirini Kaiserli, Daniel J. Gibbs
{"title":"VRN2-PRC2 facilitates light-triggered repression of PIF signaling to coordinate growth in Arabidopsis","authors":"Rory Osborne, Anne-Marie Labandera, Alex J. Ryder, Anastasia Kanali, Tianyuan Xu, Oluwatunmise Akintewe, Maximillian A. Schwarze, Christian D. Morgan, Sjon Hartman, Eirini Kaiserli, Daniel J. Gibbs","doi":"10.1016/j.devcel.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.001","url":null,"abstract":"VERNALIZATION2 (VRN2) is a flowering plant-specific subunit of the polycomb-repressive complex 2 (PRC2), a conserved eukaryotic holoenzyme that represses gene expression by depositing the histone H3 lysine 27 trimethylation (H3K27me3) mark in chromatin. Previous work established VRN2 as an oxygen-regulated target of the N-degron pathway that may function as a sensor subunit connecting PRC2 activity to the perception of endogenous and environmental cues. Here, we show that VRN2 is enriched in the hypoxic shoot apex and emerging leaves of <em>Arabidopsis</em>, where it negatively regulates growth by establishing a stable and conditionally repressed chromatin state in key PHYTOCHROME INTERACTING FACTOR (PIF)-regulated genes that promote cell expansion. This function is required to keep these genes poised for repression via a light-responsive signaling cascade later in leaf development. Thus, we identify VRN2-PRC2 as a core component of a developmentally and spatially encoded epigenetic mechanism that coordinates plant growth through facilitating the signal-dependent suppression of PIF signaling.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"27 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703190","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}