Development最新文献_第3页

Mouse ICSI impairs fertility of male offspring by disruption of fetomaternal tolerance. 小鼠ICSI通过破坏母胎耐受性而损害雄性后代的生育能力。

IF 3.6 2区生物学

Development Pub Date : 2026-05-01 Epub Date: 2026-05-07 DOI: 10.1242/dev.205500

Mito Kanatsu-Shinohara, Yusuke Shiromoto, Narumi Ogonuki, Kimiko Inoue, Keiji Mochida, Kenji Kabashima, Yingyi Kong, Shinya Toyokuni, Takuya Yamamoto, Atsuo Ogura, Takashi Shinohara

{"title":"Mouse ICSI impairs fertility of male offspring by disruption of fetomaternal tolerance.","authors":"Mito Kanatsu-Shinohara, Yusuke Shiromoto, Narumi Ogonuki, Kimiko Inoue, Keiji Mochida, Kenji Kabashima, Yingyi Kong, Shinya Toyokuni, Takuya Yamamoto, Atsuo Ogura, Takashi Shinohara","doi":"10.1242/dev.205500","DOIUrl":"https://doi.org/10.1242/dev.205500","url":null,"abstract":"Intracytoplasmic sperm injection (ICSI) is widely used to treat human infertility, yet its effects on offspring fertility remain unclear. As infertile gametes are used in human ICSI procedures, it has remained unclear whether the procedure per se influences fertility of the resulting offspring. Here, we report on increased abortion rates and the induction of immunotolerance breakdown in mice following ICSI. Although sperm concentration was normal, sperm from ICSI-derived males showed higher curvilinear velocity and greater amplitude of lateral head displacement, suggesting a potentially increased fertilization capacity. However, when ICSI-produced males were naturally mated with wild-type females, 27.1% of the fetuses were aborted, compared to a loss of 7.5% of fetuses in control pregnancies, despite identical H2 haplotypes. Analysis of the placenta revealed infiltrating macrophages and granulocytes, as well as increased levels of 8-oxoguanine. This was accompanied by activation of innate immunity and significant downregulation of microRNAs located in the Dlk1-Dio3 microRNA cluster. Several organs of the grand-offspring exhibited inflammation. Therefore, ICSI procedure using wild-type gametes impairs the fertility of ICSI-derived male offspring by activating innate immunity during pregnancy.","PeriodicalId":11375,"journal":{"name":"Development","volume":"153 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vertebrate endoderm development. 脊椎动物的内胚层发育。

IF 3.6 2区生物学

Development Pub Date : 2026-05-01 DOI: 10.1242/dev.205164

Bailey A T Weatherbee, Scott A Rankin, Aaron M Zorn

引用次数: 0

The people behind the papers - Mito Kanatsu-Shinohara. 报纸背后的人，水户金津筱原。

IF 3.6 2区生物学

Development Pub Date : 2026-05-01 Epub Date: 2026-05-07 DOI: 10.1242/dev.205753

引用次数: 0

Microcephaly-associated genes asp and Sas4 influence chromatin organization and nuclear lamina structure in Drosophila melanogaster. 小头症相关基因asp和Sas4影响黑腹果蝇的染色质组织和核层结构。

IF 3.6 2区生物学

Development Pub Date : 2026-05-01 DOI: 10.1242/dev.205125

Degisew Yinur Mengistu, Marta Marzullo, Claudia Pellacani, Marcella Marchetti, Marta Terribili, Emma Montivero Morales, Maria Patrizia Somma, Laura Ciapponi

{"title":"Microcephaly-associated genes asp and Sas4 influence chromatin organization and nuclear lamina structure in Drosophila melanogaster.","authors":"Degisew Yinur Mengistu, Marta Marzullo, Claudia Pellacani, Marcella Marchetti, Marta Terribili, Emma Montivero Morales, Maria Patrizia Somma, Laura Ciapponi","doi":"10.1242/dev.205125","DOIUrl":"https://doi.org/10.1242/dev.205125","url":null,"abstract":"Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by reduced brain size and intellectual disability. Mutations in over 30 genes, nearly half linked to centrosome biogenesis or microtubule (MT) dynamics, highlight spindle defects in disease aetiology, yet these alone do not fully explain MCPH. Here we show that the Drosophila orthologs of ASPM/MCPH5 (asp) and CENPJ/MCPH6 (Sas4) contribute to safeguard nuclear architecture and chromatin organization during brain development. Loss of either gene perturbs MT organization and centromere clustering, leading to reduced Lamin and HP1α levels and deformed nuclear lamina. Mutants also display a global reduction in heterochromatin-associated histone marks, H3K9me2/3 and H3K27me3, along with an increase in the euchromatin-associated mark H3K4me3 and elevated DNA damage with delayed repair. Notably, inhibiting demethylases with Methylstat restores H3K9me3 and nuclear morphology. These findings suggest a novel role for centrosome proteins in regulating chromatin organization, providing new insights into the mechanisms underlying MCPH pathogenesis.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PTEN regulates starburst amacrine cell dendrite morphology during development. 在发育过程中，PTEN调节星爆无突细胞的树突形态。

IF 3.6 2区生物学

Development Pub Date : 2026-05-01 Epub Date: 2026-05-07 DOI: 10.1242/dev.204980

Teva W Bracha, Nina Luong, Joseph Leffler, Benjamin Sivyer, Kevin M Wright

{"title":"PTEN regulates starburst amacrine cell dendrite morphology during development.","authors":"Teva W Bracha, Nina Luong, Joseph Leffler, Benjamin Sivyer, Kevin M Wright","doi":"10.1242/dev.204980","DOIUrl":"10.1242/dev.204980","url":null,"abstract":"Neurons are subject to extensive developmental regulation to ensure precise subtype-specific morphologies that are intimately tied to their function. Starburst amacrine cells (SACs) in the mammalian retina have a highly stereotyped, radially symmetric dendritic arbor that is essential for their role in direction-selective circuits in the retina. We show that PTEN, the primary negative regulator of the PI3K-AKT-mTOR pathway that is highly implicated in neurodevelopmental disorders, regulates SAC morphology in a cell-autonomous manner. Pten-deficient mouse SACs show a nearly twofold increase in the number of dendritic branches, while other morphological properties remain largely unchanged. These morphological changes arise late in SAC development, after dendrite development is largely complete, and persist into adulthood. Mechanistically, excessive dendritic branching appears to arise from dysregulated mTOR activity. Despite this increase in dendritic branches, Pten-deficient SACs maintain a normal population number, normal organization of synaptic outputs and intact direction-selectivity in the retina. Collectively, these results show that PTEN is essential in mouse for the normal development of highly stereotyped neuronal morphology.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-dimensional regulation of LIN-28 temporal expression dynamics in the C. elegans heterochronic gene cascade. 线虫异慢性基因级联中LIN-28时间表达动态的多维调控

IF 3.6 2区生物学

Development Pub Date : 2026-05-01 DOI: 10.1242/dev.205391

Charles Nelson, Victor Ambros

{"title":"Multi-dimensional regulation of LIN-28 temporal expression dynamics in the C. elegans heterochronic gene cascade.","authors":"Charles Nelson, Victor Ambros","doi":"10.1242/dev.205391","DOIUrl":"10.1242/dev.205391","url":null,"abstract":"LIN-28 is an evolutionarily conserved RNA-binding protein critical for regulating pluripotency and cell fate determination during animal development. In Caenorhabditis elegans, lin-28 is an integral component of the heterochronic (developmental timing) gene regulatory cascade. Loss-of-function mutations in lin-28 cause precocious cell fate determination during larval development. Previous studies indicate that proper progression of larval stage-specific cell fates relies on the downregulation of LIN-28, which is negatively regulated by the lin-4 microRNA through complementary sequences in the lin-28 3' UTR. This study employs CRISPR/Cas9 editing of the endogenous lin-28 locus to demonstrate that developmental downregulation of LIN-28 involves multiple inputs, including the action of the let-7 family and lin-4 microRNAs via adjacent complementary sites in the lin-28 3' UTR, along with post-translational inhibition of LIN-28 by the lep-5 long non-coding RNA, collectively accounting for nearly all LIN-28 repression. Additionally, systematic testing of truncations of the lin-28 3' UTR identifies three positive regulatory regions that enhance LIN-28 expression, counteracting the negative effects of the let-7 and lin-4 microRNAs and the lep-5 long non-coding RNA.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brassinosteroid controls leaf air space patterning non-cell autonomously by promoting epidermal growth. 油菜素内酯通过促进表皮生长来自主控制叶片空气空间模式。

IF 3.6 2区生物学

Development Pub Date : 2026-04-24 DOI: 10.1242/dev.205110

James M Fitzsimons, Ana B Rock, Richard L De Falbe, Samantha Fox, Chris D Whitewoods

{"title":"Brassinosteroid controls leaf air space patterning non-cell autonomously by promoting epidermal growth.","authors":"James M Fitzsimons, Ana B Rock, Richard L De Falbe, Samantha Fox, Chris D Whitewoods","doi":"10.1242/dev.205110","DOIUrl":"https://doi.org/10.1242/dev.205110","url":null,"abstract":"Plant leaves contain a complex network of intercellular air spaces, which allow efficient photosynthesis. However, how leaf air spaces are patterned is poorly understood. It has been proposed for almost a century that air spaces form by faster-growing epidermal tissue pulling slower growing mesophyll cells apart, but this has never been tested. Here we characterise air space morphogenesis throughout in the first leaf of A. thaliana and show that the plant hormone brassinosteroid (BR) is required for air space expansion in the palisade, but not the spongy, mesophyll. We also show that epidermal brassinosteroid perception is sufficient to promote air space expansion in the palisade non cell-autonomously and propose that this non cell-autonomous effect is due to altered epidermal growth. To test if epidermal growth affects air space patterning we reduce growth specifically in the epidermis using inducible expression of the growth repressor BIG BROTHER and show that an epidermal growth restriction reduces air space expansion in the palisade mesophyll. Overall, we propose that brassinosteroid signalling promotes growth in the epidermis to pattern air spaces in the palisade mesophyll.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Divergent temporal control of deltoid tuberosity and limb tendon development by an evolutionarily conserved Scleraxis enhancer. 一个进化保守的巩膜增强子对三角肌结节和肢体肌腱发育的发散性时间控制。

IF 3.6 2区生物学

Development Pub Date : 2026-04-24 DOI: 10.1242/dev.205325

Shinsei Yambe, Kenta Sumiyama, Hitomi Watanabe, Aki Takimoto, Takako Sasaki, Gen Kondoh, Denitsa Docheva, Chisa Shukunami

{"title":"Divergent temporal control of deltoid tuberosity and limb tendon development by an evolutionarily conserved Scleraxis enhancer.","authors":"Shinsei Yambe, Kenta Sumiyama, Hitomi Watanabe, Aki Takimoto, Takako Sasaki, Gen Kondoh, Denitsa Docheva, Chisa Shukunami","doi":"10.1242/dev.205325","DOIUrl":"https://doi.org/10.1242/dev.205325","url":null,"abstract":"Scleraxis (Scx) is a basic helix-loop-helix transcription factor predominantly expressed in tendons, ligaments, and their attachment sites, where it regulates maturation. Here, we report a novel Scx enhancer that drives tissue-specific expression. In transgenic reporter mice, a 5.3 kb downstream Scx enhancer (dSE) conferred robust, stable, and faithful reporter activity reproducing the endogenous Scx expression pattern. Within the dSE, we identified a 343 bp Scx enhancer (CSE), conserved from lobe-finned fishes to tetrapods, that recapitulates Scx expression in limbs. In developing limbs, CSE-deficient mice exhibited a marked reduction of endogenous Scx expression and a complete loss of the deltoid tuberosity (DT) supporting forelimb leverage, accompanied by attenuated BMP and TGF-b signaling, as in Scx-deficient mice. Precise enhancer activation within a critical developmental window was indispensable for DT formation. In contrast, tendon/ligament maturation retained prolonged plasticity, with Scx expression partially recovering later, likely through additional elements within the dSE. These findings uncover an essential role of the CSE in DT morphogenesis and reveal distinct temporal enhancer requirements for DT versus tendon/ligament formation, with additional enhancer dependence confined to tendons/ligaments.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endothelial von hippel-lindau deletion causes abnormal blood and lymphatic vasculature through ectopic activation of HIF-CXCR4 axis. 内皮细胞希佩尔-林道缺失通过HIF-CXCR4轴的异位激活导致血液和淋巴血管异常。

IF 3.6 2区生物学

Development Pub Date : 2026-04-20 DOI: 10.1242/dev.204519

Wenling Li, Koh Nakayama, Ryo Sato, Rina Shimada, Yoshiaki Kubota, Yoh-Suke Mukouyama

{"title":"Endothelial von hippel-lindau deletion causes abnormal blood and lymphatic vasculature through ectopic activation of HIF-CXCR4 axis.","authors":"Wenling Li, Koh Nakayama, Ryo Sato, Rina Shimada, Yoshiaki Kubota, Yoh-Suke Mukouyama","doi":"10.1242/dev.204519","DOIUrl":"https://doi.org/10.1242/dev.204519","url":null,"abstract":"The Von Hippel-Lindau (VHL) protein regulates cellular oxygen sensing by degrading hypoxia-inducible factors (HIFs) under normoxic conditions. VHL mutations show highly vascularized tumor across various organs due to HIF activation and upregulation of HIF-target genes such as VEGF in non-endothelial cells (ECs), influencing neighboring ECs and triggering abnormal angiogenesis. Whether VHL mutations in ECs also contribute to abnormal angiogenesis remains unclear. To address this question, we utilized a well-characterized skin vasculature model, which encompasses the processes of vascular patterning and arterial/venous development, to investigate vascular development in mice with an EC-specific VHL deletion. The mutants exhibited abnormal vascular network formation and embryonic lethal. Mechanistically, the VHL deletion led to ectopic expression of the chemokine receptor CXCR4 through HIF stabilization in ECs. Treatment with AMD3100, a CXCR4 antagonist, partially restored vascular abnormalities caused by VHL deletion in ECs. Additionally, publicly available single-cell RNA-sequencing data from ECs of patients with VHL syndrome supports our findings, indicating that VHL mutations in ECs contribute to abnormal angiogenesis through ectopic activation of the HIF-CXCR4 signaling axis.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PLAC1 possesses fundamental and unique roles in regulating rat and human trophoblast cell development. PLAC1在调节大鼠和人滋养细胞发育中具有基础和独特的作用。

IF 3.6 2区生物学

Development Pub Date : 2026-04-20 DOI: 10.1242/dev.205290

Ayelen Moreno-Irusta, Jovana Urosevic, Khursheed Iqbal, Arun S Seetharam, Jackson Nteeba, Regan L Scott, Marija Kuna, Masanaga Muto, Keisuke Kozai, Andjelka Celic, Hiroaki Okae, Takahiro Arima, David K Johnson, Geetu Tuteja, Michael J Soares

{"title":"PLAC1 possesses fundamental and unique roles in regulating rat and human trophoblast cell development.","authors":"Ayelen Moreno-Irusta, Jovana Urosevic, Khursheed Iqbal, Arun S Seetharam, Jackson Nteeba, Regan L Scott, Marija Kuna, Masanaga Muto, Keisuke Kozai, Andjelka Celic, Hiroaki Okae, Takahiro Arima, David K Johnson, Geetu Tuteja, Michael J Soares","doi":"10.1242/dev.205290","DOIUrl":"https://doi.org/10.1242/dev.205290","url":null,"abstract":"Placenta enriched 1 (PLAC1) is a conserved X chromosome-linked gene expressed in the mammalian placenta. We investigated the biology of PLAC1 in the rat and human placenta. Plac1 transcripts were expressed in the junctional zone of the rat placenta and in intrauterine invasive trophoblast cells. Genome-edited Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, a deficiency of intrauterine invasive trophoblast cells, and a late gestation stage uterine-placental interface infiltrated with natural killer cells. PLAC1 facilitated rat trophoblast cell differentiation. In contrast, PLAC1 showed minimal contributions to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Furthermore, PLAC1 impacts on cellular function were linked to furin, paired basic amino acid cleaving enzyme (FURIN), in rat and human trophoblast cells. Thus, PLAC1 is critically involved in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0