Pub Date : 2024-11-01DOI: 10.1016/j.devcel.2024.10.006
Xixi Cai, Hang Zhang, Changqing Mu, Yanjun Chen, Chongzhen He, Mingyu Liu, Thomas Laux, Limin Pi
In multicellular organisms, communication between cells is vital for their fate determination. In plants, the quiescent center (QC) signals to adjacent stem cells to maintain them undifferentiated. However, how surrounding stem cells instruct the QC remains poorly understood. Here, we show that in the Arabidopsis root, microRNA160 (miR160) moves from stele stem cells (SSCs) to the QC, where it degrades the mRNAs of two auxin response factors, ARF10 and ARF17. This degradation relieves BRAVO from direct transcriptional repression, maintaining QC quiescence. We further identify that blocking miR160 movement due to DNA damage-induced SSC death and restricted symplastic transport reduces BRAVO and WOX5 expression, leading to QC division to replenish damaged stem cells during root regeneration. Together, our results demonstrate that a transcriptional axis initiated by mobile miR160 regulates the QC and stem cell behavior, advancing our understanding of the communication between stem cells and their surrounding cellular environment.
{"title":"A mobile miR160-triggered transcriptional axis controls root stem cell niche maintenance and regeneration in Arabidopsis","authors":"Xixi Cai, Hang Zhang, Changqing Mu, Yanjun Chen, Chongzhen He, Mingyu Liu, Thomas Laux, Limin Pi","doi":"10.1016/j.devcel.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.006","url":null,"abstract":"In multicellular organisms, communication between cells is vital for their fate determination. In plants, the quiescent center (QC) signals to adjacent stem cells to maintain them undifferentiated. However, how surrounding stem cells instruct the QC remains poorly understood. Here, we show that in the <em>Arabidopsis</em> root, microRNA160 (miR160) moves from stele stem cells (SSCs) to the QC, where it degrades the mRNAs of two auxin response factors, <em>ARF10</em> and <em>ARF17</em>. This degradation relieves <em>BRAVO</em> from direct transcriptional repression, maintaining QC quiescence. We further identify that blocking miR160 movement due to DNA damage-induced SSC death and restricted symplastic transport reduces <em>BRAVO</em> and <em>WOX5</em> expression, leading to QC division to replenish damaged stem cells during root regeneration. Together, our results demonstrate that a transcriptional axis initiated by mobile miR160 regulates the QC and stem cell behavior, advancing our understanding of the communication between stem cells and their surrounding cellular environment.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"87 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562138","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 : 2024-10-30DOI: 10.1016/j.devcel.2024.10.004
Rinaldo Catta-Preta, Susan Lindtner, Athena Ypsilanti, Nicolas Seban, James D. Price, Armen Abnousi, Linda Su-Feher, Yurong Wang, Karol Cichewicz, Sally A. Boerma, Ivan Juric, Ian R. Jones, Jennifer A. Akiyama, Ming Hu, Yin Shen, Axel Visel, Len A. Pennacchio, Diane E. Dickel, John L.R. Rubenstein, Alex S. Nord
Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as in vivo enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.
转录因子（TF）与顺式调控元件组合结合，协调转录程序。尽管对染色质状态和染色体相互作用的研究已经展示了动态的神经发育顺式调控景观，但对TF相互作用的平行理解却相对滞后。为了阐明驱动小鼠基底节发育的TF组合结合，我们整合了12种TF的染色质免疫沉淀测序（ChIP-seq）、H3K4me3相关的增强子-启动子相互作用、染色质和基因表达数据以及功能增强子测定。我们发现了几组具有共享TF结合的推定调控元件（TF-pRE模块），它们协调GABA能神经发生的不同过程并抑制其他细胞命运。大多数 pRE 被一个或两个 TF 结合；但也有一小部分被广泛结合。这些序列具有特殊的进化保守性和主题密度、复杂的染色体相互作用以及作为体内增强子的活性。我们的研究结果提供了对在端脑神经发生过程中激活和抑制表达程序的组合 TF-pRE 相互作用的见解，并证明了 TF 结合对发育转录线路建模的价值。
{"title":"Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis","authors":"Rinaldo Catta-Preta, Susan Lindtner, Athena Ypsilanti, Nicolas Seban, James D. Price, Armen Abnousi, Linda Su-Feher, Yurong Wang, Karol Cichewicz, Sally A. Boerma, Ivan Juric, Ian R. Jones, Jennifer A. Akiyama, Ming Hu, Yin Shen, Axel Visel, Len A. Pennacchio, Diane E. Dickel, John L.R. Rubenstein, Alex S. Nord","doi":"10.1016/j.devcel.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.004","url":null,"abstract":"Transcription factors (TFs) bind combinatorially to <em>cis</em>-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental <em>cis</em>-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as <em>in vivo</em> enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"26 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542100","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}
Understanding the cellular and genetic mechanisms driving human-specific features of cortical development remains a challenge. We generated a cell-type resolved atlas of transcriptome and chromatin accessibility in the developing macaque and mouse prefrontal cortex (PFC). Comparing with published human data, our findings demonstrate that although the cortex cellular composition is overall conserved across species, progenitor cells show significant evolutionary divergence in cellular properties. Specifically, human neural progenitors exhibit extensive transcriptional rewiring in growth factor and extracellular matrix (ECM) pathways. Expression of the human-specific progenitor marker ITGA2 in the fetal mouse cortex increases the progenitor proliferation and the proportion of upper-layer neurons. These transcriptional divergences are primarily driven by altered activity in the distal regulatory elements. The chromatin regions with human-gained accessibility are enriched with human-specific sequence changes and polymorphisms linked to intelligence and neuropsychiatric disorders. Our results identify evolutionary changes in neural progenitors and putative gene regulatory mechanisms shaping primate brain evolution.
{"title":"Comparative single-cell multiome identifies evolutionary changes in neural progenitor cells during primate brain development","authors":"Yuting Liu, Xin Luo, Yiming Sun, Kaimin Chen, Ting Hu, Benhui You, Jiahao Xu, Fengyun Zhang, Qing Cheng, Xiaoyu Meng, Tong Yan, Xiang Li, Xiaoxuan Qi, Xiechao He, Xuejiang Guo, Cheng Li, Bing Su","doi":"10.1016/j.devcel.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.005","url":null,"abstract":"Understanding the cellular and genetic mechanisms driving human-specific features of cortical development remains a challenge. We generated a cell-type resolved atlas of transcriptome and chromatin accessibility in the developing macaque and mouse prefrontal cortex (PFC). Comparing with published human data, our findings demonstrate that although the cortex cellular composition is overall conserved across species, progenitor cells show significant evolutionary divergence in cellular properties. Specifically, human neural progenitors exhibit extensive transcriptional rewiring in growth factor and extracellular matrix (ECM) pathways. Expression of the human-specific progenitor marker <em>ITGA2</em> in the fetal mouse cortex increases the progenitor proliferation and the proportion of upper-layer neurons. These transcriptional divergences are primarily driven by altered activity in the distal regulatory elements. The chromatin regions with human-gained accessibility are enriched with human-specific sequence changes and polymorphisms linked to intelligence and neuropsychiatric disorders. Our results identify evolutionary changes in neural progenitors and putative gene regulatory mechanisms shaping primate brain evolution.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"2 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541582","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 : 2024-10-29DOI: 10.1016/j.devcel.2024.10.003
Roni Levin-Konigsberg, Koushambi Mitra, Kaitlyn Spees, AkshatKumar Nigam, Katherine Liu, Camille Januel, Pravin Hivare, Sophia M. Arana, Laura M. Prolo, Anshul Kundaje, Manuel D. Leonetti, Yamuna Krishnan, Michael C. Bassik
Ammonia is a ubiquitous, toxic by-product of cell metabolism. Its high membrane permeability and proton affinity cause ammonia to accumulate inside acidic lysosomes in its poorly membrane-permeant form: ammonium (NH4+). Ammonium buildup compromises lysosomal function, suggesting the existence of mechanisms that protect cells from ammonium toxicity. Here, we identified SLC12A9 as a lysosomal-resident protein that preserves organelle homeostasis by controlling ammonium and chloride levels. SLC12A9 knockout (KO) cells showed grossly enlarged lysosomes and elevated ammonium content. These phenotypes were reversed upon removal of the metabolic source of ammonium or dissipation of the lysosomal pH gradient. Lysosomal chloride increased in SLC12A9 KO cells, and chloride binding by SLC12A9 was required for ammonium transport. Our data indicate that SLC12A9 function is central for the handling of lysosomal ammonium and chloride, an unappreciated, fundamental mechanism of lysosomal physiology that may have special relevance in tissues with elevated ammonia, such as tumors.
{"title":"An SLC12A9-dependent ion transport mechanism maintains lysosomal osmolarity","authors":"Roni Levin-Konigsberg, Koushambi Mitra, Kaitlyn Spees, AkshatKumar Nigam, Katherine Liu, Camille Januel, Pravin Hivare, Sophia M. Arana, Laura M. Prolo, Anshul Kundaje, Manuel D. Leonetti, Yamuna Krishnan, Michael C. Bassik","doi":"10.1016/j.devcel.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.003","url":null,"abstract":"Ammonia is a ubiquitous, toxic by-product of cell metabolism. Its high membrane permeability and proton affinity cause ammonia to accumulate inside acidic lysosomes in its poorly membrane-permeant form: ammonium (NH<sub>4</sub><sup>+</sup>). Ammonium buildup compromises lysosomal function, suggesting the existence of mechanisms that protect cells from ammonium toxicity. Here, we identified SLC12A9 as a lysosomal-resident protein that preserves organelle homeostasis by controlling ammonium and chloride levels. SLC12A9 knockout (KO) cells showed grossly enlarged lysosomes and elevated ammonium content. These phenotypes were reversed upon removal of the metabolic source of ammonium or dissipation of the lysosomal pH gradient. Lysosomal chloride increased in SLC12A9 KO cells, and chloride binding by SLC12A9 was required for ammonium transport. Our data indicate that SLC12A9 function is central for the handling of lysosomal ammonium and chloride, an unappreciated, fundamental mechanism of lysosomal physiology that may have special relevance in tissues with elevated ammonia, such as tumors.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536561","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 : 2024-10-25DOI: 10.1016/j.devcel.2024.10.002
D. Nathaniel Clarke, Pearson W. Miller, Adam C. Martin
The movements that give rise to the body’s structure are powered by cell shape changes and rearrangements that are coordinated at supracellular scales. How such cellular coordination arises and integrates different morphogenetic programs is unclear. Using quantitative imaging, we found a complex pattern of adherens junction (AJ) levels in the ectoderm prior to gastrulation onset in Drosophila. AJ intensity exhibited a double-sided gradient, with peaks at the dorsal midline and ventral neuroectoderm. We show that this dorsal-ventral AJ pattern is regulated by epidermal growth factor (EGF) signaling and that this signal is required for ectoderm cell movement during mesoderm invagination and axis extension. We identify AJ levels and junctional actomyosin as downstream effectors of EGFR signaling. Overall, our study demonstrates an EGF-patterned mechanical feedback mechanism that coordinates tissue folding and convergent extension to facilitate embryo-wide gastrulation movements.
细胞形状的变化和重新排列在超细胞尺度上进行协调，是形成人体结构的运动的动力。这种细胞协调如何产生并整合不同的形态发生程序尚不清楚。利用定量成像技术，我们发现果蝇在开始胃形成之前，外胚层的粘连接头（AJ）水平呈现出复杂的模式。AJ 强度呈现双侧梯度，峰值位于背侧中线和腹侧神经外胚层。我们的研究表明，这种背侧-腹侧 AJ 模式受表皮生长因子（EGF）信号调控，在中胚层内陷和轴延伸过程中，外胚层细胞移动需要这种信号。我们发现 AJ 水平和交界肌动蛋白是表皮生长因子信号的下游效应因子。总之，我们的研究证明了一种以 EGF 为模式的机械反馈机制，它能协调组织折叠和会聚延伸，从而促进整个胚胎的胃形成运动。
{"title":"EGFR-dependent actomyosin patterning coordinates morphogenetic movements between tissues in Drosophila melanogaster","authors":"D. Nathaniel Clarke, Pearson W. Miller, Adam C. Martin","doi":"10.1016/j.devcel.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.002","url":null,"abstract":"The movements that give rise to the body’s structure are powered by cell shape changes and rearrangements that are coordinated at supracellular scales. How such cellular coordination arises and integrates different morphogenetic programs is unclear. Using quantitative imaging, we found a complex pattern of adherens junction (AJ) levels in the ectoderm prior to gastrulation onset in <em>Drosophila</em>. AJ intensity exhibited a double-sided gradient, with peaks at the dorsal midline and ventral neuroectoderm. We show that this dorsal-ventral AJ pattern is regulated by epidermal growth factor (EGF) signaling and that this signal is required for ectoderm cell movement during mesoderm invagination and axis extension. We identify AJ levels and junctional actomyosin as downstream effectors of EGFR signaling. Overall, our study demonstrates an EGF-patterned mechanical feedback mechanism that coordinates tissue folding and convergent extension to facilitate embryo-wide gastrulation movements.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"5 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489628","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 : 2024-10-25DOI: 10.1016/j.devcel.2024.10.001
Anna Geiselmann, Adèle Micouin, Sandrine Vandormael-Pournin, Vincent Laville, Almira Chervova, Sébastien Mella, Pablo Navarro, Michel Cohen-Tannoudji
The inner cell mass (ICM) of early mouse embryos is specified into epiblast (Epi) and primitive endoderm (PrE) lineages during blastocyst formation. The antagonistic transcription factors (TFs) NANOG and GATA-binding protein 6 (GATA6) in combination with fibroblast growth factor (FGF)/extracellular-signal-regulated kinase (ERK) signaling are central actors in ICM fate choice. However, what initiates the specification of ICM progenitors into Epi or PrE and whether other factors are involved in this process has not been fully understood yet. Here, we show that phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) is constitutively active during preimplantation development. Using pharmacological inhibition, we demonstrate that PI3K/AKT enables the formation of a functional ICM capable of giving rise to both the Epi and the PrE: it maintains the expression of the TF NANOG, which specifies the Epi, and confers responsiveness to FGF4, which is essential for PrE specification. Our work thus identifies PI3K/AKT signaling as an upstream regulator controlling the molecular events required for both Epi and PrE specification.
{"title":"PI3K/AKT signaling controls ICM maturation and proper epiblast and primitive endoderm specification in mice","authors":"Anna Geiselmann, Adèle Micouin, Sandrine Vandormael-Pournin, Vincent Laville, Almira Chervova, Sébastien Mella, Pablo Navarro, Michel Cohen-Tannoudji","doi":"10.1016/j.devcel.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.001","url":null,"abstract":"The inner cell mass (ICM) of early mouse embryos is specified into epiblast (Epi) and primitive endoderm (PrE) lineages during blastocyst formation. The antagonistic transcription factors (TFs) NANOG and GATA-binding protein 6 (GATA6) in combination with fibroblast growth factor (FGF)/extracellular-signal-regulated kinase (ERK) signaling are central actors in ICM fate choice. However, what initiates the specification of ICM progenitors into Epi or PrE and whether other factors are involved in this process has not been fully understood yet. Here, we show that phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) is constitutively active during preimplantation development. Using pharmacological inhibition, we demonstrate that PI3K/AKT enables the formation of a functional ICM capable of giving rise to both the Epi and the PrE: it maintains the expression of the TF NANOG, which specifies the Epi, and confers responsiveness to FGF4, which is essential for PrE specification. Our work thus identifies PI3K/AKT signaling as an upstream regulator controlling the molecular events required for both Epi and PrE specification.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"144 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489626","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 : 2024-10-18DOI: 10.1016/j.devcel.2024.09.025
David Grommisch, Harald Lund, Evelien Eenjes, Anais Julien, Christian Göritz, Robert A. Harris, Rickard Sandberg, Michael Hagemann-Jensen, Maria Genander
Regionalized disease prevalence is a common feature of the gastrointestinal tract. Herein, we employed regionally resolved Smart-seq3 single-cell sequencing, generating a comprehensive cell atlas of the adult mouse esophagus. Characterizing the esophageal axis, we identify non-uniform distribution of epithelial basal cells, fibroblasts, and immune cells. In addition, we demonstrate a position-dependent, but cell subpopulation-independent, transcriptional signature, collectively generating a regionalized esophageal landscape. Combining in vivo models with organoid co-cultures, we demonstrate that proximal and distal basal progenitor cell states are functionally distinct. We find that proximal fibroblasts are more permissive for organoid growth compared with distal fibroblasts and that the immune cell profile is regionalized in two dimensions, where proximal-distal and epithelial-stromal gradients impact epithelial maintenance. Finally, we predict and verify how WNT, BMP, insulin growth factor (IGF), and neuregulin (NRG) signaling are differentially engaged along the esophageal axis. We establish a cellular and transcriptional framework for understanding esophageal regionalization, providing a functional basis for epithelial disease susceptibility.
{"title":"Regionalized cell and gene signatures govern esophageal epithelial homeostasis","authors":"David Grommisch, Harald Lund, Evelien Eenjes, Anais Julien, Christian Göritz, Robert A. Harris, Rickard Sandberg, Michael Hagemann-Jensen, Maria Genander","doi":"10.1016/j.devcel.2024.09.025","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.09.025","url":null,"abstract":"Regionalized disease prevalence is a common feature of the gastrointestinal tract. Herein, we employed regionally resolved Smart-seq3 single-cell sequencing, generating a comprehensive cell atlas of the adult mouse esophagus. Characterizing the esophageal axis, we identify non-uniform distribution of epithelial basal cells, fibroblasts, and immune cells. In addition, we demonstrate a position-dependent, but cell subpopulation-independent, transcriptional signature, collectively generating a regionalized esophageal landscape. Combining <em>in vivo</em> models with organoid co-cultures, we demonstrate that proximal and distal basal progenitor cell states are functionally distinct. We find that proximal fibroblasts are more permissive for organoid growth compared with distal fibroblasts and that the immune cell profile is regionalized in two dimensions, where proximal-distal and epithelial-stromal gradients impact epithelial maintenance. Finally, we predict and verify how WNT, BMP, insulin growth factor (IGF), and neuregulin (NRG) signaling are differentially engaged along the esophageal axis. We establish a cellular and transcriptional framework for understanding esophageal regionalization, providing a functional basis for epithelial disease susceptibility.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"5 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448380","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 : 2024-10-17DOI: 10.1016/j.devcel.2024.09.026
Lijie Xuan, Jiayi Li, Yupeng Jiang, Meiqi Shi, Yunke Zhu, Xinru Bao, Qingqiu Gong, Hong-wei Xue, Hao Yu, Lu Liu
The plant hormone auxin orchestrates almost all aspects of plant growth and development. AUXIN RESPONSE FACTORs (ARFs) control the transcription of auxin-responsive genes, forming cytoplasmic condensates to modulate auxin sensitivity and diversify auxin response regulation. However, the dynamic control of ARF distribution across different subcellular compartments remains largely obscure. Here, we show that three MULTIPLE C2 DOMAIN AND TRANSMEMBRANE REGION PROTEINs (MCTPs), MCTP3, MCTP4, and MCTP6, control ARF nucleocytoplasmic partitioning and determine lateral root development. MCTP3/4/6 are highly expressed in lateral roots and specifically interact with ARF7 and ARF19 to dissolve their cytoplasmic condensates. This promotes ARF nuclear localization in lateral root primordia and enhances auxin signaling during lateral root formation. Our findings confer MCTP as a key switch to modulate auxin responses and outline an MCTP-ARF signaling cascade that is crucial for the establishment of the plant root system.
{"title":"MCTP controls nucleocytoplasmic partitioning of AUXIN RESPONSE FACTORs during lateral root development","authors":"Lijie Xuan, Jiayi Li, Yupeng Jiang, Meiqi Shi, Yunke Zhu, Xinru Bao, Qingqiu Gong, Hong-wei Xue, Hao Yu, Lu Liu","doi":"10.1016/j.devcel.2024.09.026","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.09.026","url":null,"abstract":"The plant hormone auxin orchestrates almost all aspects of plant growth and development. AUXIN RESPONSE FACTORs (ARFs) control the transcription of auxin-responsive genes, forming cytoplasmic condensates to modulate auxin sensitivity and diversify auxin response regulation. However, the dynamic control of ARF distribution across different subcellular compartments remains largely obscure. Here, we show that three MULTIPLE C2 DOMAIN AND TRANSMEMBRANE REGION PROTEINs (MCTPs), MCTP3, MCTP4, and MCTP6, control ARF nucleocytoplasmic partitioning and determine lateral root development. MCTP3/4/6 are highly expressed in lateral roots and specifically interact with ARF7 and ARF19 to dissolve their cytoplasmic condensates. This promotes ARF nuclear localization in lateral root primordia and enhances auxin signaling during lateral root formation. Our findings confer MCTP as a key switch to modulate auxin responses and outline an MCTP-ARF signaling cascade that is crucial for the establishment of the plant root system.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"11 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444072","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 : 2024-10-17DOI: 10.1016/j.devcel.2024.09.029
Jun Zheng, Jing Chen, Zhihe Cao, Kaichen Wu, Jinhui Wang, Yusong Guo, Min Zhuang
Peroxisome biogenesis involves two pathways: growth and division from pre-existing mature peroxisomes and de novo biogenesis from the endoplasmic reticulum, with a contribution from mitochondria, particularly in human peroxisome-deficient cells. However, the essential components that control peroxisome de novo biogenesis are largely unknown. Dual organelle localized ubiquitin ligase MARCH5 functions on peroxisomes to control pexophagy. Here, we show that mitochondria-localized MARCH5 is essential for the formation of vesicles in the de novo biogenesis of peroxisomes from mitochondria in human cell lines. Loss of MARCH5 specifically impedes the budding of PEX3-containing vesicles from mitochondria, thereby blocking the formation of pre-peroxisomes. Overall, our study highlights the function of MARCH5 for mitochondria-derived pre-peroxisomes, emphasizing MARCH5 as one regulator to maintain peroxisome homeostasis.
{"title":"Ubiquitin ligase MARCH5 controls the formation of mitochondria-derived pre-peroxisomes","authors":"Jun Zheng, Jing Chen, Zhihe Cao, Kaichen Wu, Jinhui Wang, Yusong Guo, Min Zhuang","doi":"10.1016/j.devcel.2024.09.029","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.09.029","url":null,"abstract":"Peroxisome biogenesis involves two pathways: growth and division from pre-existing mature peroxisomes and <em>de novo</em> biogenesis from the endoplasmic reticulum, with a contribution from mitochondria, particularly in human peroxisome-deficient cells. However, the essential components that control peroxisome <em>de novo</em> biogenesis are largely unknown. Dual organelle localized ubiquitin ligase MARCH5 functions on peroxisomes to control pexophagy. Here, we show that mitochondria-localized MARCH5 is essential for the formation of vesicles in the <em>de novo</em> biogenesis of peroxisomes from mitochondria in human cell lines. Loss of MARCH5 specifically impedes the budding of PEX3-containing vesicles from mitochondria, thereby blocking the formation of pre-peroxisomes. Overall, our study highlights the function of MARCH5 for mitochondria-derived pre-peroxisomes, emphasizing MARCH5 as one regulator to maintain peroxisome homeostasis.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"66 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444127","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 : 2024-10-17DOI: 10.1016/j.devcel.2024.09.010
Nicolas Verhoeven, Yumiko Oshima, Etienne Cartier, Claudia Christiane Bippes, Albert Neutzner, Liron Boyman, Mariusz Karbowski
We report that the outer mitochondrial membrane (OMM)-associated E3 Ub ligase MARCH5 is vital for generating mitochondria-derived pre-peroxisomes. In human immortalized cells, MARCH5 knockout leads to the accumulation of immature peroxisomes, reduced fatty-acid-induced peroxisomal biogenesis, and abnormal peroxisome biogenesis in MARCH5/Pex14 and MARCH5/Pex3 dko cells. Upon fatty-acid-induced peroxisomal biogenesis, MARCH5 redistributes to peroxisomes, and ubiquitination activity-deficient mutants of MARCH5 accumulate on peroxisomes containing high levels of the OMM protein Tom20 (mitochondria-derived pre-peroxisomes). Similarly, depletion of peroxisome biogenesis factor Pex14 leads to the accumulation of MARCH5- and Tom20-positive pre-peroxisomes, whereas no peroxisomes are detected in MARCH5/Pex14 dko cells. Inconsistent with MARCH5 merely acting as a quality factor, mitochondrial decline is not evident in tested models. Furthermore, reduced expression of peroxisomal proteins is detected in MARCH5−/− cells, whereas some of these proteins are stabilized in peroxisome biogenesis deficiency models lacking MARCH5 expression. Thus, MARCH5 is central for mitochondria-dependent peroxisome biogenesis.
{"title":"Outer mitochondrial membrane E3 Ub ligase MARCH5 controls de novo peroxisome biogenesis","authors":"Nicolas Verhoeven, Yumiko Oshima, Etienne Cartier, Claudia Christiane Bippes, Albert Neutzner, Liron Boyman, Mariusz Karbowski","doi":"10.1016/j.devcel.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.09.010","url":null,"abstract":"We report that the outer mitochondrial membrane (OMM)-associated E3 Ub ligase MARCH5 is vital for generating mitochondria-derived pre-peroxisomes. In human immortalized cells, MARCH5 knockout leads to the accumulation of immature peroxisomes, reduced fatty-acid-induced peroxisomal biogenesis, and abnormal peroxisome biogenesis in MARCH5/Pex14 and MARCH5/Pex3 dko cells. Upon fatty-acid-induced peroxisomal biogenesis, MARCH5 redistributes to peroxisomes, and ubiquitination activity-deficient mutants of MARCH5 accumulate on peroxisomes containing high levels of the OMM protein Tom20 (mitochondria-derived pre-peroxisomes). Similarly, depletion of peroxisome biogenesis factor Pex14 leads to the accumulation of MARCH5- and Tom20-positive pre-peroxisomes, whereas no peroxisomes are detected in MARCH5/Pex14 dko cells. Inconsistent with MARCH5 merely acting as a quality factor, mitochondrial decline is not evident in tested models. Furthermore, reduced expression of peroxisomal proteins is detected in MARCH5<sup>−/−</sup> cells, whereas some of these proteins are stabilized in peroxisome biogenesis deficiency models lacking MARCH5 expression. Thus, MARCH5 is central for mitochondria-dependent peroxisome biogenesis.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"17 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444070","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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