Developmental Dynamics最新文献_第8页

Spatiotemporal dynamics of mTORC1 and mTORC2 in the developing spinal cord and their essential roles in gliogenesis. mTORC1和mTORC2在脊髓发育中的时空动态及其在胶质瘤发生中的重要作用。

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-21 DOI: 10.1002/dvdy.70150

Rina Sasaki, Noriaki Sasai, Takuma Shinozuka

{"title":"Spatiotemporal dynamics of mTORC1 and mTORC2 in the developing spinal cord and their essential roles in gliogenesis.","authors":"Rina Sasaki, Noriaki Sasai, Takuma Shinozuka","doi":"10.1002/dvdy.70150","DOIUrl":"https://doi.org/10.1002/dvdy.70150","url":null,"abstract":"Background: Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase with diverse roles in development and homeostasis, but its spatiotemporal dynamics in the embryonic spinal cord are not fully defined. Here, we map mTOR activity across mouse spinal cord development and test its function using a conditional gene mutant.Results: Immunohistochemistry for phosphorylated readouts of mTORC1 and mTORC2 revealed distinct, stage-dependent patterns. In the early neural tube, phosphorylated S6 (p-S6; Ser235/236 and Ser240/244) marked dorsal progenitors and ventral motor neurons, while p-p70S6K, p-4E-BP1, and p-Akt (Ser473) were enriched along the luminal surface where mitoses occur. By E13.5, p-S6 persisted in the motor column, whereas p-p70S6K, p-4E-BP1, and luminal p-Akt remained ventricular; at E18.5, robust p-S6 and p-p70S6K signals were localized to neuronal somata and fibers in the marginal layer, with minimal p-Akt. Closer examination revealed that mTORC1/2 signals preferentially colocalized with pHH3-positive ventricular progenitors early, then decoupled as development progressed. Within motor neurons, mTORC1 broadly overlapped with Islet1, including the Lhx3-positive medial motor column (MMC), whereas mTORC2 (p-Akt) labeled an Islet1-positive subset complementary to Lhx3 and declined over time, demarcating lateral, non-MMC domains. Nestin-Cre-mediated mTOR deletion did not overtly affect neuronal organization but reduced GFAP- and Sox10-positive glial lineage cells, indicating a selective requirement of mTOR for glial differentiation.Conclusions: Together, the data suggest separable and temporal roles of mTORC1 and mTORC2 in progenitor mitosis, motor-neuron domain organization, and late embryonic gliogenesis.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

BOOPTHAT: An inexpensive and scalable system for spatiotemporal activation of heat-shock transgenes in zebrafish. BOOPTHAT：一种廉价且可扩展的系统，用于斑马鱼热休克转基因的时空激活。

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-20 DOI: 10.1002/dvdy.70152

Darren Wang, Benjamin L Martin

{"title":"BOOPTHAT: An inexpensive and scalable system for spatiotemporal activation of heat-shock transgenes in zebrafish.","authors":"Darren Wang, Benjamin L Martin","doi":"10.1002/dvdy.70152","DOIUrl":"10.1002/dvdy.70152","url":null,"abstract":"Background: Gaining finer spatiotemporal control over gene expression is critical for unraveling the regulatory networks that coordinate embryogenesis. While the heat-shock inducible gene expression system is a widely used tool for controlling temporal transgene expression, its applicability in spatiotemporal control is limited.Results: We present the BOOPTHAT (Batch-Operating Optically Powered Targeted Heater for Activating Transgenes) as a low-cost system for activating heat-shock inducible transgenes with spatiotemporal control in multiple zebrafish embryos at a time. The BOOPTHAT system is built from 3D printed components and inexpensive consumer parts. Independent 3D printed micromanipulators are used to position optical fiber probes. When coupled to a light source, the probes are heated photothermally and are used to perform targeted gene activation in multiple samples at a time.Conclusions: By adding a level of spatial control onto the well-established system of heat-shock inducible transgenes, we take advantage of the existing infrastructure surrounding the heat-shock induction system and introduce new ways to use the multitude of existing lines. We demonstrate the capabilities of our system and highlight some areas of research that stand to benefit from this frugal and effective system.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Loss of POGLUT2/3-mediated O-glucosylation produces lung and aortic phenotypes reminiscent of fibrillin1 mutants. poglut2 /3介导的o糖基化缺失会产生与纤原蛋白1突变体相似的肺和主动脉表型。

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-19 DOI: 10.1002/dvdy.70148

Sanjiv Neupane, Angelina Almiroudis, Kaitlyn E Donnelly, Robert S Haltiwanger, Bernadette C Holdener

{"title":"Loss of POGLUT2/3-mediated O-glucosylation produces lung and aortic phenotypes reminiscent of fibrillin1 mutants.","authors":"Sanjiv Neupane, Angelina Almiroudis, Kaitlyn E Donnelly, Robert S Haltiwanger, Bernadette C Holdener","doi":"10.1002/dvdy.70148","DOIUrl":"https://doi.org/10.1002/dvdy.70148","url":null,"abstract":"Background: Fibrillins provide a scaffold for elastic fiber formation, which enables lung recoil and aortic compliance. Abnormal fibrillin microfibrils, as in Marfan syndrome, lead to enlarged alveoli, vascular stiffening, and aneurysms. Our earlier studies suggested that fibrillin function depends on O-glucosylation of its epidermal growth factor (EGF)-like repeats by protein O-glucosyltransferase 2 (POGLUT2) and 3 (POGLUT3). Mice lacking both enzymes (Poglut2/3 DKO) die soon after birth. Rare survivors are runted, have digit 2-3 syndactyly, and variable eye defects. Here, we wanted to determine whether O-glucosylation was important for fibrillin organization/function during lung and aorta development.Results: Fibrillin microfibrils and elastic fibrils were reduced and disorganized in the Poglut2/3 DKO lung and aorta. In the lung, loss of O-glucosylation impaired airway branching, delayed sacculation, and postnatally caused mildly enlarged alveolar airspaces and reduced lipofibroblasts and capillary endothelial cells. In the ascending aorta, the Poglut2/3 DKO led to disorganized smooth muscle layers with increased nuclear YAP, potentially indicating a change in matrix stiffness.Conclusions: The lung and aorta defects in Poglut2/3 DKO resembled mouse Fbn1 and Ltbp mutant models, suggesting a common microfibril-driven mechanism. Future studies should examine how loss of fibrillin O-glucosylation affects microfibril-dependent regulation of TGF-β and BMP signaling and matrix biomechanics.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

An accessible microfluidic perfusion platform for time-restricted control of zebrafish embryonic patterning. 用于斑马鱼胚胎模式限时控制的可访问微流控灌注平台。

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-19 DOI: 10.1002/dvdy.70151

Mohammed Nakhuda, M Fethullah Simsek

{"title":"An accessible microfluidic perfusion platform for time-restricted control of zebrafish embryonic patterning.","authors":"Mohammed Nakhuda, M Fethullah Simsek","doi":"10.1002/dvdy.70151","DOIUrl":"https://doi.org/10.1002/dvdy.70151","url":null,"abstract":"Understanding the dynamic nature of developmental networks requires live imaging techniques capable of capturing real-time developmental processes in wild-type and mutant embryos as they are exposed to pharmacological perturbations. A peculiar developmental patterning process in early vertebrate embryos is the sequential segmentation of bilateral somites from the unsegmented tail tissue along their major axis. Earlier work discovered that segmentation is instructed by an oscillatory fibroblast growth factor (Fgf)/ERK signaling gradient sourced from the tailbud. Somite segmentation was recapitulated at will in the absence of the molecular oscillator, \"the segmentation clock\", via pulsatile drug inhibitions. Here, we present a live imaging setup for zebrafish embryos that incorporates a 3D-printed chamber and a programmed syringe pump for precise, automated, periodic drug delivery. The chamber secures the orientation of zebrafish embryos in agarose inserts and incorporates inflow and outflow ports to facilitate controlled drug perfusion. Servo motors controlled by an Arduino were integrated to automate valve switching, achieving fully automated exchange of two different fluids for alternating drug delivery and rinse cycles. Such periodic delivery of an inhibitor drug entrains the Fgf/ERK signaling gradient in the embryonic tail to oscillate in clock-deficient mutants, creating lab-reconstituted somites in otherwise defective embryos. Embryos expressing fluorescent markers can further be imaged at single-cell resolution during perturbations. Overall, this system provides a cost-effective, reproducible platform for investigating vertebrate development and interrogating cellular decision-making under controlled experimental conditions. We anticipate this setup will be broadly beneficial for the biomedical research community interested in controlled drug delivery and in vivo cellular dynamics.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Meet the Editorial Team. An interview with Angelo Iulianella, Assistant Editor, Dalhousie University Faculty of Medicine, Canada. 见见编辑团队。专访加拿大达尔豪斯大学医学院助理编辑安杰洛·尤利亚内拉。

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-14 DOI: 10.1002/dvdy.70139

Paul Trevorrow, Angelo Iulianella

引用次数: 0

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-12

引用次数: 0

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-12

引用次数: 0

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-12

引用次数: 0

Mutations in KAT3 family of lysine acetyl transferases impair neural crest migration in Rubinstein Taybi syndrome models. 赖氨酸乙酰转移酶KAT3家族突变影响Rubinstein Taybi综合征模型的神经嵴迁移。

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-11 DOI: 10.1002/dvdy.70144

Shweta Verma, Sujit Dalabehera, Subhash Gowda, Koushika Chandrasekaran, Dayanidhi Singh, Bhavana Prasher, Sharmila Bapat, Sivaprakash Ramalingam, Chetana Sachidanandan

{"title":"Mutations in KAT3 family of lysine acetyl transferases impair neural crest migration in Rubinstein Taybi syndrome models.","authors":"Shweta Verma, Sujit Dalabehera, Subhash Gowda, Koushika Chandrasekaran, Dayanidhi Singh, Bhavana Prasher, Sharmila Bapat, Sivaprakash Ramalingam, Chetana Sachidanandan","doi":"10.1002/dvdy.70144","DOIUrl":"https://doi.org/10.1002/dvdy.70144","url":null,"abstract":"Background: Rubinstein Taybi syndrome (RSTS), a rare congenital disease, is caused by mutations in lysine acetyl transferase type 3 (KAT3) genes, EP300 and CREBBP. Many of the tissues affected in RSTS are derived from the neural crest (NC). Hence, we proposed that NC development would be perturbed in RSTS.Results: Zebrafish RSTS models generated by knocking down or mutating ep300a and crebbpa genes reveal defects in NC migration. This effect on migration is conserved in NC cells generated from human RSTS patient-derived induced pluripotent stem cells (iPSC) cells. The defects in NC migration can be partially reversed by HDAC inhibition in morphant embryos. KAT3 knockdown causes downregulation of snai1b and snai2 and upregulation of cdh6, important regulators of epithelial to mesenchymal transition (EMT). Snai2 is known to repress CDH6, also known as cadherin 6b, in chick NC cells facilitating their delamination from the neural tube and migration.Conclusions: We demonstrate for the first time that NC migration is defective in zebrafish and iPSC models of RSTS. We make a case for classifying RSTS as a neurocristopathy. We propose that KAT3 genes control NC migration through regulation of EMT genes snai2 and snai1b.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Proteomic profiling of Elp1-deficient trigeminal ganglia reveals disruption of neurotrophic and metabolic pathways in a familial dysautonomia mouse model. elp1缺陷三叉神经节的蛋白质组学分析揭示了家族性自主神经障碍小鼠模型中神经营养和代谢途径的破坏。

IF 1.5 3区生物学

Developmental Dynamics Pub Date : 2026-05-10 DOI: 10.1002/dvdy.70145

Carrie E Leonard, Lauren Clarissa Tang, Beatrix Ueberheide, Lisa A Taneyhill

{"title":"Proteomic profiling of Elp1-deficient trigeminal ganglia reveals disruption of neurotrophic and metabolic pathways in a familial dysautonomia mouse model.","authors":"Carrie E Leonard, Lauren Clarissa Tang, Beatrix Ueberheide, Lisa A Taneyhill","doi":"10.1002/dvdy.70145","DOIUrl":"https://doi.org/10.1002/dvdy.70145","url":null,"abstract":"Background: Elp1, a subunit of the Elongator complex, is essential for tRNA modification and neuronal development. Mutations in ELP1 underlie familial dysautonomia (FD), a disorder marked by sensory and autonomic neuropathy. While loss of Elp1 disrupts trigeminal ganglion formation and survival, the downstream molecular consequences remain poorly defined.Results: We performed quantitative proteomic profiling of trigeminal ganglia from Elp1 conditional knockout (CKO) and control embryos at E13.5. Across 5650 detected proteins, 25 were significantly up-regulated and 26 down-regulated in Elp1 CKO embryos. EnrichR analysis revealed enrichment of up-regulated proteins in amino acid transport and tRNA aminoacylation pathways, with links to neuromuscular and neuropathic diseases. Down-regulated proteins were associated with RNA modification, cholesterol biosynthesis, and synaptic organization. Validation by immunohistochemistry confirmed decreased expression of the neurotrophic receptor Gfra3 and the neuropeptide Galanin, and increased levels of the chromatin regulator Chd1, in Elp1 CKO embryos relative to controls.Conclusions: These findings demonstrate that Elp1 loss disrupts metabolic, RNA modification, and neurotrophic signaling pathways in the developing trigeminal ganglion. Proteomic analysis thus provides new insight into the molecular consequences of Elp1 deficiency and highlights candidate mechanisms contributing to sensory neuron vulnerability in FD.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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