Development最新文献_第5页

Loss of arap3 drives a cerebral cavernous malformation-like phenotype in zebrafish via Krit1 interaction and RhoA dysregulation. arap3的缺失通过Krit1相互作用和RhoA失调驱动斑马鱼的脑海绵状畸形样表型。

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-21 DOI: 10.1242/dev.205762

Di Yang, Zewen Tao, Si Chen, Hongcheng Wang, Lingfei Luo, Jingying Chen

{"title":"Loss of arap3 drives a cerebral cavernous malformation-like phenotype in zebrafish via Krit1 interaction and RhoA dysregulation.","authors":"Di Yang, Zewen Tao, Si Chen, Hongcheng Wang, Lingfei Luo, Jingying Chen","doi":"10.1242/dev.205762","DOIUrl":"https://doi.org/10.1242/dev.205762","url":null,"abstract":"Cerebral cavernous malformations (CCMs) are severe vascular anomalies characterized by abnormal cerebrovascular development, leading to profound structural and functional deficits in the brain. However, the exact underlying mechanisms driving CCM pathogenesis remain incompletely understood. In this study, we identify a zebrafish arap3 mutant that exhibits localized vascular dilation, cerebral hemorrhage, impaired vascular network formation and reduced mural cell coverage - phenotypes that collectively and strikingly recapitulate the key pathological features of clinical CCM. We demonstrate that arap3 is highly enriched in cerebrovascular endothelial cells, and its deficiency severely impairs endothelial cell polarity and overall vascular homeostasis. Mechanistically, arap3 contributes to CCM pathogenesis through the dysregulation of RhoA GTPase activity. Furthermore, we provide compelling evidence physically and functionally linking Arap3 to the CCM signaling complex by demonstrating that Arap3 interacts with Krit1 (CCM1). Our findings establish a crucial framework for understanding the etiology of CCM and present a highly trackable in vivo model for the future discovery of targeted therapeutics.","PeriodicalId":11375,"journal":{"name":"Development","volume":"153 18","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012039","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

In preprints - is birth driving cortical maturation? 在预印本中——出生是否推动了大脑皮层的成熟？

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-17 DOI: 10.1242/dev.206042

Veronica Pravata, Clarisse Brunet Avalos

引用次数: 0

Early glucagon-positive cells restrict pancreatic branching through VMAT2-noradrenaline-mediated ROS signaling. 早期胰高血糖素阳性细胞通过vmat2 -去甲肾上腺素介导的ROS信号传导限制胰腺分支。

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-11 DOI: 10.1242/dev.205734

Airi Inoue, Fumiya Uefune, Takahiro Shitamichi, Daisuke Sakano, Shoen Kume

{"title":"Early glucagon-positive cells restrict pancreatic branching through VMAT2-noradrenaline-mediated ROS signaling.","authors":"Airi Inoue, Fumiya Uefune, Takahiro Shitamichi, Daisuke Sakano, Shoen Kume","doi":"10.1242/dev.205734","DOIUrl":"10.1242/dev.205734","url":null,"abstract":"Vesicular monoamine transporter 2 (VMAT2) transports monoamines into storage vesicles. We have previously reported that VMAT2 negatively regulates pancreatic progenitor differentiation into endocrine beta cells; however, the underlying mechanism remains unknown. Using a pancreatic bud explant culture, we show here that inhibiting VMAT2-mediated catecholamine uptake promotes pancreatic epithelial branching and increases the number of insulin-expressing cells. The increase in pancreatic branching was mimicked by inhibition of tyrosine hydroxylase, monoamine oxidase A, dopamine beta-hydroxylase or norepinephrine transporter. RNA sequencing analysis of the pancreatic buds revealed that reactive oxygen species (ROS) play a role in branch formation. We found that these early glucagon (GCG) and insulin (INS) co-expressing cells express VMAT2 and monoamine signaling components. Lineage-specific VMAT2 deletion in Gcg-expressing cells resulted in increased pancreatic branching and islet areas, and decreased ROS accumulation. We conclude that early GCG and INS co-expressing cells regulate pancreatic branching morphogenesis via VMAT2-noradrenaline-mediated ROS signaling.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817849","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

Single-nucleus multiome sequencing reveals the molecular basis of thermal acclimation in Drosophila melanogaster embryos. 单核多组测序揭示了黑腹果蝇胚胎热驯化的分子基础。

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-28 DOI: 10.1242/dev.205729

Thomas S O'Leary, Emily E Mikucki, Sumaetee Tangwancharoen, Joseph R Boyd, Sara Helms Cahan, Seth Frietze, Brent L Lockwood

{"title":"Single-nucleus multiome sequencing reveals the molecular basis of thermal acclimation in Drosophila melanogaster embryos.","authors":"Thomas S O'Leary, Emily E Mikucki, Sumaetee Tangwancharoen, Joseph R Boyd, Sara Helms Cahan, Seth Frietze, Brent L Lockwood","doi":"10.1242/dev.205729","DOIUrl":"10.1242/dev.205729","url":null,"abstract":"Embryogenesis is remarkably robust to temperature variability, yet the homeostatic mechanisms that offset thermal effects during early development remain poorly understood. We measured how acclimation shifts the upper thermal limit and profiled chromatin accessibility and gene expression in Drosophila melanogaster embryos using single-nucleus multiome sequencing. Acclimation preserved shared primordial cell types yet rapidly shifted heat tolerance. Cool-acclimated embryos showed a homeostatic response characterized by increased accessibility at binding motifs for the transcriptional activator Zelda, along with enhanced activity of gene regulatory networks in a subset of primordial cell types, including the gut, muscle and nervous system. Cool-acclimated embryos also had higher expression of ribosomal and oxidative phosphorylation genes, suggesting a coordinated increase in translation and energy production to buffer slower biochemical kinetics in the cold. Our results indicate that maintaining developmental robustness across temperature requires homeostatic gene expression responses that may carry metabolic costs constraining upper thermal limits.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963058","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

PLC-IP3 signaling promotes sensory hair cell formation in zebrafish neuromast. PLC-IP3信号通路促进斑马鱼神经肥大感觉毛细胞的形成。

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-11 DOI: 10.1242/dev.205705

Chao Yang, Fuping Qian, Jie Gong, Xin Wang, Dong Liu

{"title":"PLC-IP3 signaling promotes sensory hair cell formation in zebrafish neuromast.","authors":"Chao Yang, Fuping Qian, Jie Gong, Xin Wang, Dong Liu","doi":"10.1242/dev.205705","DOIUrl":"10.1242/dev.205705","url":null,"abstract":"Sensorineural hearing loss primarily results from irreversible damage to sensory hair cells (HCs), and regenerative strategies remain limited by inefficient HC formation and incomplete functional maturation of newly generated cells. Here, using pharmacological perturbation, single-cell transcriptomics sequencing, and genetic analysis in zebrafish neuromasts, we identify phosphoinositide-specific phospholipase C (PLC) signaling as an intracellular regulator of HC development and maturation. Activation of PLC signaling increases the number of HCs and FM4-64 labeling, whereas inhibition reduces HC number and impairs sensory-driven behavior. Single-cell trajectory and RNA velocity analyses reveal that PLC signaling does not alter lineage topology, but promotes progression along the HC differentiation trajectory. Among PLC isoforms, plcd4a is selectively enriched in HCs and is necessary to promote HC formation and maturation. Mechanistically, pathway perturbation experiments suggest that PLC-IP3 signaling functionally interacts with Notch and Wnt pathways during HC differentiation. Together, these findings support a model in which PLC signaling promotes HC differentiation and maturation-associated progression, providing insight into mechanisms that may promote HC regeneration.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910995","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

Pathway to Independence - an interview with Swarnabh Bhattacharya (Zico). 独立之路——采访Swarnabh Bhattacharya （Zico）

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-21 DOI: 10.1242/dev.206103

引用次数: 0

In preprints - 'slow and steady' versus 'fast and ready' (re)generation of insulin-expressing cells in zebrafish. 在预印本中——斑马鱼中胰岛素表达细胞的“缓慢而稳定”和“快速而准备”（重新）生成。

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-17 DOI: 10.1242/dev.206041

Olov Andersson, Jiarui Mi, Qianqian Ma

引用次数: 0

Two distributed enhancers of Sox17 additively regulate the developmental fate of bipotential ventral pancreato-biliary progenitor cells. Sox17的两个分布式增强子加在一起调节双电位腹侧胰胆祖细胞的发育命运。

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-18 DOI: 10.1242/dev.205751

Ryan R Finnel, Jessica R Musselman, Margaret E McFadden, Isabella M Silvestri, Jennifer Skelton, Leesa L Sampson, Anna B Osipovich, Christopher V E Wright, Mark A Magnuson

{"title":"Two distributed enhancers of Sox17 additively regulate the developmental fate of bipotential ventral pancreato-biliary progenitor cells.","authors":"Ryan R Finnel, Jessica R Musselman, Margaret E McFadden, Isabella M Silvestri, Jennifer Skelton, Leesa L Sampson, Anna B Osipovich, Christopher V E Wright, Mark A Magnuson","doi":"10.1242/dev.205751","DOIUrl":"10.1242/dev.205751","url":null,"abstract":"SRY-box transcription factor 17 (Sox17) is essential for hepato-pancreato-biliary development. We identified two distributed enhancers of Sox17, Sox17e-13 and Sox17e-231, within the likely murine Sox17 topologically associating domain. Individual CRISPR-mediated enhancer deletions temporally reduce endodermal Sox17 expression, delaying the transition of bipotent ventral pancreato-biliary progenitor cells to a lineage-unipotent ventral pancreatic fate, reducing pancreas size and increasing gallbladder size. Deleting both enhancers further reduces Sox17 expression and delays conversion of bipotent progenitor cells to ventral pancreatic or biliary fates, reducing both pancreas and gallbladder size. Crossing each enhancer mutation to a Sox17 null allele revealed differential and profound sensitivities of the extrahepatic biliary system to alterations of Sox17 expression, as demonstrated by gallbladder hypoplasia, gallbladder agenesis with a cystic duct, and biliary atresia. These studies indicate that Sox17e-13 and Sox17e-231 additively modulate Sox17 expression, that the differentiation of bipotential ventral pancreato-biliary cells to unipotent fates is Sox17 dosage dependent, and that thresholds for Sox17 action during pancreato-biliary formation vary by developmental stage, further defining the role of Sox17 in hepato-pancreato-biliary formation and function.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864100","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

Pathway to Independence - an interview with Josep Mercadal. 独立之路-约瑟普·梅卡达尔访谈。

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-18 DOI: 10.1242/dev.206065

引用次数: 0

The curious case of the placental genome. 胎盘基因组的奇特案例。

IF 4 2区生物学

Development Pub Date : 2026-09-15 Epub Date: 2026-09-24 DOI: 10.1242/dev.205800

Zoé Ducarne, Agathe Chaigne, My Anh Truong

{"title":"The curious case of the placental genome.","authors":"Zoé Ducarne, Agathe Chaigne, My Anh Truong","doi":"10.1242/dev.205800","DOIUrl":"https://doi.org/10.1242/dev.205800","url":null,"abstract":"The human placenta is among the few, if not the only, healthy mammalian tissues that may exploit a cancer-like somatic genome for its function. Acting simultaneously as the lungs, kidneys, liver and gastrointestinal tract, the placenta mediates nutrient and gas exchange, blocks out toxins and pathogens, removes fetal waste, and secretes hormones essential for pregnancy. Recent research has revealed that the placenta is a genomically distinctive organ with an unusually high mutational load, abundant structural variations, prevalent aneuploidy and genome amplification, as well as a tissue-sized multinucleated syncytium. These features may underlie its invasiveness and high levels of cell proliferation, as well as its dual role as both exchange platform and barrier between mother and fetus. Here, we review our current understanding of the unique genomic features of the human placenta and their potential functions. We identify prevalent gaps in current literature and suggest new research directions to address the need for a better understanding of placental genomics. Such understanding has the potential to inform clinical diagnostic and management strategies for pregnancy complications, thereby improving pregnancy outcomes.","PeriodicalId":11375,"journal":{"name":"Development","volume":"153 18","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037117","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