Developmental biology最新文献_第6页

Evaluation of molecular interaction studies of khellin on bovine serum albumin through various biophysical approaches 不同生物物理方法对大灰莲与牛血清白蛋白分子相互作用研究的评价。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-16 DOI: 10.1016/j.ydbio.2025.11.008

Sowmya Priya Manoharan , Suvathika Gnanaselvan , Suriya Prakash Ramakrishnan , Sangilimuthu Alagar Yadav , L. Srimathi Priya , Manikandan Ayyar , Lalitha Gnanasekaran , M. Santhamoorthy , S. Santhoshkumar

The understanding of how drugs interact with carrier proteins is crucial in the field of pharmacology and the life sciences, especially in the field of drug invention. In the present work described the molecular interaction of pharmaceutically important phyto-molecule khellin on bovine serum albumin. Khellin is recognized for its ability to widen blood vessels, making it useful for heart health. It's a major component of the plant Ammi visnaga and Dioscorea species helps to protect the heart. Bovine serum albumin (BSA) is a model protein of Human serum albumin hence, BSA has been used for drug-binding properties studies. Various biophysical techniques to examine the interactions between khellin and BSA. The biophysical techniques such as fluorescence quenching by fluorescence spectroscopy studies, micro-environmental changes by synchronous fluorescence, protein structural changes by circular dichroism spectroscopy, molecular docking, ADMET properties studies, SWISS Target Prediction for target analysis and pharmacokinetic analysis by insilico. The Khellin-BSA interaction was examined using fluorescence analysis, which showed that the binding constant was 1.29 ± 0.2 × 10¹² M⁻¹ and binding free energy was −7.99 kcal/mol by in vitro. The binding energy was compared with computation molecular docking studies of ligand and protein interaction showed the binding energy of −5.1 kcal/mol. It is nearer to the in vitro binding energy values of khellin on BSA. The micro-environmental changes of the ligand-protein complex were observed with peak shifts at Δλ15 for tyrosine, Δλ60 for tryptophane, and Δλ90 for phenylalanine. Also, the secondary structural changes of BSA after titrating the khellin were observed and found that there were secondary structural changes in the free BSA after adding the khellin. With possible targets found through SWISS Target Prediction, khellin is a promising druggable candidate, according to ADMET analysis, which revealed zero violations. Finally, we concluded that the Phyto-active constituent khellin possesses good binding affinity on BSA. Further, it can be taken for drug discovery experiments on clinical trials.

了解药物如何与载体蛋白相互作用在药理学和生命科学领域，特别是在药物发明领域是至关重要的。本文描述了具有重要药用意义的植物分子赫氏蛋白与牛血清白蛋白的分子相互作用。海胆碱被认为具有扩张血管的能力，对心脏健康有益。它是一种主要成分的植物和薯蓣物种有助于保护心脏。牛血清白蛋白（BSA）是人血清白蛋白的模型蛋白，已被用于药物结合特性的研究。利用各种生物物理技术来研究贝壳蛋白和牛血清白蛋白之间的相互作用。利用荧光光谱技术研究荧光猝灭、同步荧光技术研究微环境变化、圆二色光谱技术研究蛋白质结构变化、分子对接、ADMET性质研究、SWISS Target Prediction进行靶标分析、insilico进行药代动力学分析等生物物理技术。荧光分析表明，Khellin-BSA的结合常数为1.29±0.2 × 1012 M-1，结合自由能为-7.99 kcal/mol。配体与蛋白质相互作用的分子对接研究显示结合能为-5.1 kcal/mol。它更接近于大肠杆菌在BSA上的离体结合能值。观察到配体-蛋白复合物的微环境变化，酪氨酸为Δλ15，色氨酸为Δλ60，苯丙氨酸为Δλ90出现峰移。同时，我们还观察了在加入海藻素后游离BSA的二级结构变化，发现加入海藻素后游离BSA发生了二级结构变化。根据ADMET的分析，通过SWISS靶标预测发现可能的靶标，khellin是一种很有前途的候选药物，该分析显示零违规。最后，我们得出结论，植物活性成分khellin对BSA具有良好的结合亲和力。还可用于临床试验的药物发现实验。

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引用次数: 0

PDGFRα is required for postnatal cerebral perivascular fibroblast development “PDGFRα是出生后大脑血管周围成纤维细胞发育所必需的”。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-14 DOI: 10.1016/j.ydbio.2025.11.003

Hannah E. Jones , Kelsey A. Abrams , Sol Kim , Katherine A. Fantauzzo , Julie A. Siegenthaler

Perivascular fibroblasts (PVFs) are a cell type associated with large diameter blood vessels in the brain and spinal cord parenchyma and leptomeninges. PVFs have previously defined roles in injury and neuroinflammatory diseases and predicted roles in supporting neurovascular function. The temporal dynamics of PVF development in the pre- and postnatal cerebral cortex have recently been described, however the molecular mechanisms that underly PVF development have not been identified. PVFs express both platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ. Here we investigate the role of PDGF signaling in PVF development. We use immunohistochemistry and RNA transcript detection methods to show developmental expression of PDGFRs by PVFs and examine distribution of PDGF ligand expression in the brain. We show that postnatal deletion of PDGFRα in fibroblasts using the Col1a2-CreERT mouse line impairs PVF coverage of cerebral vessels at postnatal day 10. Perivascular macrophages, a cell type previously shown to co-develop with PVFs, have impaired cerebral vessel coverage in conditional mutants that is similar to PVF coverage defects. This work establishes a requirement for PDGFRα signaling in PVF development and may shed light upon the potential pathways that are over-activated in PVFs in injury and disease contexts.

血管周围成纤维细胞（PVFs）是一种与大直径血管和脊髓实质及轻脑膜相关的细胞类型。PVFs在损伤和神经炎症性疾病中有明确的作用，并预测其在支持神经血管功能中的作用。PVF在产前和产后大脑皮层发育的时间动态最近已经被描述，但是PVF发育的分子机制尚未被确定。PVFs表达血小板衍生生长因子受体（PDGFRs）、PDGFRα和PDGFRβ。在这里，我们研究PDGF信号在PVF发展中的作用。我们使用免疫组织化学和RNA转录检测方法来显示PVFs对pdgfr的发育表达，并检测PDGF配体在脑中的表达分布。我们使用Col1a2-CreERT小鼠系发现，出生后成纤维细胞中PDGFRα的缺失会在出生后第10天损害脑血管PVF的覆盖。血管周围巨噬细胞，一种先前被证明与PVF共同发育的细胞类型，在条件突变体中损害了脑血管覆盖，类似于PVF覆盖缺陷。这项工作建立了PDGFRα信号在PVF发展中的需求，并可能揭示在损伤和疾病背景下PVF过度激活的潜在途径。

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引用次数: 0

RNA redistribution driven by alterations in transcription during early embryogenesis of rainbow trout 虹鳟鱼早期胚胎发生过程中转录改变驱动的RNA再分配。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-14 DOI: 10.1016/j.ydbio.2025.11.004

Katerina Cihakova , Ravindra Naraine , Viktoriia Hantzsch , Roman Franek , Martin Psenicka , Radek Sindelka

In many species, the differential localization of RNAs along the animal-vegetal axis is established during oogenesis. The resulting asymmetry is essential for axis formation, germ layer patterning, and cell fate determination, especially in fish and amphibians. In recent years, research in this field has focused mainly on zebrafish, which raises the question about the conservation of localization processes across all teleost species. Although extant teleost species utilize meroblastic cleavage only, there are extreme differences in their oocyte size. These differences are fundamentally linked to each species' life history. Some have rapid embryonic development, while embryos of other species, like salmonids, take weeks to develop. This might have consequences on the spatial distribution of biomolecules during oogenesis and their relocalization during early embryogenesis. Yet, our knowledge is based on data from small-sized oocyte species with rapid development only (e.g. zebrafish). In this study, we performed a spatially resolved TOMO-seq method on early embryos of the rainbow trout, a species characterized by prolonged embryonic development and large oocytes, and compared it with zebrafish. We revealed that the maternal pre-patterned localization of transcripts can be disrupted in the early embryo by two main mechanisms: de novo transcription and degradation. The most prominent change can be seen in the emerging blastodisc in the animal pole, where there is a significant increase in localized transcripts. In contrast with research suggesting active relocalization of RNAs by ooplasmic streaming in zebrafish, we hypothesized that the change in RNA localization is caused by regionalized zygotic transcription in trout. Regardless of these differing mechanisms, the cross-species comparison revealed a conservation of many transcripts involved in germ cell development and cell proliferation. Moreover, using hybrid trout embryos, we were able to reveal the early onset of de novo transcription. Altogether, these findings indicate how species with large oocytes and prolonged development utilize unique RNA localization strategies. This knowledge expands our understanding of early development across teleost species.

在许多物种中，沿动物-植物轴的rna的差异定位是在卵发生期间建立的。由此产生的不对称对于轴的形成、胚层图案和细胞命运的决定至关重要，尤其是在鱼类和两栖动物中。近年来，该领域的研究主要集中在斑马鱼身上，这就提出了关于所有硬骨鱼物种定位过程保护的问题。虽然现存的硬骨鱼物种只利用元母细胞分裂，但它们的卵母细胞大小存在极大差异。这些差异与每个物种的生活史有着根本的联系。一些物种的胚胎发育迅速，而其他物种的胚胎，如鲑鱼，需要数周的时间来发育。这可能对卵发生过程中生物分子的空间分布及其在胚胎发生早期的再定位产生影响。然而，我们的知识仅基于快速发育的小型卵母细胞物种（例如斑马鱼）的数据。在这项研究中，我们对虹鳟鱼的早期胚胎进行了空间分辨TOMO-seq方法，虹鳟鱼具有胚胎发育时间长，卵母细胞大的特点，并与斑马鱼进行了比较。我们发现母体转录本的预模式定位在胚胎早期可以通过两种主要机制被破坏：从头转录和降解。最显著的变化可以在动物极的新生囊胚中看到，在那里有显著增加的局部转录本。与斑马鱼卵浆流中RNA主动再定位的研究相反，我们假设RNA定位的变化是由鳟鱼的区域化合子转录引起的。抛开这些不同的机制不谈，跨物种比较揭示了许多参与生殖细胞发育和细胞增殖的转录本的保存。此外，使用杂交鳟鱼胚胎，我们能够揭示早期开始的从头转录。总之，这些发现表明具有大卵母细胞和长时间发育的物种如何利用独特的RNA定位策略。这一知识扩展了我们对硬骨鱼物种早期发育的理解。

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引用次数: 0

Teaching developmental neurobiology with inclusion and valuing of neurodivergent learners 以包容和重视神经发散学习者的方式教授发育神经生物学。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-14 DOI: 10.1016/j.ydbio.2025.11.007

Isha Verma , R. Keith Duncan , Haylie L. Miller , Michael Uhler

Developmental biology is one of the fundamental sciences for understanding the basics of life and often intersects with social justice challenges facing society. This article describes an inclusive teaching activity for students and instructors to explore the interface between developmental biology, genetic diversity, and social justice. The instructor and students will choose a recent publication and use it as the basis for exploring the roles of specific genes characterized in autism from educational, emulative, and ethical perspectives. The assignment for students will include a discussion and demonstration of developmental neurobiology and principles of gene function within the nervous system, as well as ethical considerations for how individuals, as well as society as a whole, should consider genetic variations. Two frameworks are introduced for instructors to create an inclusive learning environment, including universal design for learning and multipartiality. Resources and examples are given throughout the article for instructors to use, and a suggested rubric is also provided. A post-activity self-reflection performed by the students will facilitate their own assessment of how the teaching activity has impacted their philosophical and social perspectives on genetic diversity. The short-term goal of the activity is to promote an immediate appreciation of neurodiversity among the participating students, and the long-term goal is to demonstrate the importance of neurodiversity for developing a just society.

发育生物学是理解生命基础的基础科学之一，经常与社会面临的社会正义挑战交叉。这篇文章描述了一个包容性的教学活动，让学生和教师探索发育生物学，遗传多样性和社会正义之间的接口。教师和学生将选择最近的出版物，并将其作为基础，从教育、竞争和伦理的角度探索自闭症中特定基因的作用。学生的作业将包括讨论和演示发育神经生物学和神经系统内基因功能的原理，以及个人和整个社会应该如何考虑遗传变异的伦理考虑。本文介绍了教师创造包容性学习环境的两种框架，包括学习的通用设计和多元偏好。整篇文章都提供了可供教师使用的参考资料和示例，还提供了一个建议的标题。学生在活动后进行的自我反思将有助于他们自己评估教学活动如何影响他们对遗传多样性的哲学和社会观点。该活动的短期目标是促进参与学生对神经多样性的即时欣赏，长期目标是展示神经多样性对发展公正社会的重要性。

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引用次数: 0

Ureteric stromal progenitors give rise to kidney inner cortical pericytes via an arterial mural cell intermediate 输尿管间质祖细胞经动脉壁细胞中间体形成肾内皮质周细胞。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-13 DOI: 10.1016/j.ydbio.2025.11.005

Peter M. Luo , Neha H. Ahuja , Thomas J. Carroll , Ondine Cleaver

During kidney formation, segmented epithelial tubules and blood vessels develop within a heterogeneous and progressively patterned stroma. By E18.5, the murine renal stroma exhibits several transcriptionally and spatially distinct populations, including specialized stromal cells associated with the vasculature, termed mural cells. However, the precise contributions of stromal progenitor lineages to this stromal heterogeneity, as well as the dynamics of renal mural cell investment, remain unclear. Previous studies have described stromal progenitors in the developing cortex that transiently express the transcription factor Foxd1, as well as stromal progenitors in the ureter that express Tbx18, and have shown that both are capable of giving rise to renal stromal cells, including vascular mural cells. Here, we use pulse induction of Tbx19CreERT2 at different timepoints to elucidate the contribution of the Tbx18 population to stromal patterning. We show that the Tbx18-lineage, when induced at E12.5, gives rise to arterial mural cells, without ever progressing through a Foxd1+ cortical stromal progenitor state. These arterial mural cells are only transiently present along arteries during development, ultimately contributing instead to peritubular capillaries. When traced post-natally, the Tbx18-lineage gives rise to pericytes, which are enriched in S3-segment-associated, Cxcl14-enriched stroma in the inner cortex. We show that these pericytes arise directly from arterial mural cells seen earlier during development. These data help clarify a small portion of the complicated lineage relationships of renal stromal progenitors and their contribution to the kidney vascular-associated mural cells.

在肾脏形成过程中，分节上皮小管和血管在异质的、逐渐定型的基质中发育。到E18.5，小鼠肾间质呈现出几个转录和空间上不同的群体，包括与脉管系统相关的特化基质细胞，称为壁细胞。然而，基质祖细胞谱系对这种基质异质性的确切贡献，以及肾壁细胞投资的动态，仍不清楚。先前的研究已经描述了输尿管中基质祖细胞的一个亚群，该亚群可瞬时表达转录因子Tbx18并产生肾基质细胞，包括血管壁细胞。利用Tbx18CreERT2在不同时间点的脉冲感应，我们阐明了这一群体对基质模式的贡献。我们发现，当tbx18谱系在E12.5诱导时，产生动脉壁细胞，而不经过Foxd1+皮质基质祖细胞状态。这些动脉壁细胞仅在动脉发育过程中短暂存在，最终形成小管周围毛细血管。当在出生后进行追踪时，tbx18谱系产生周细胞，周细胞富含与s3片段相关的内皮层中富含cxcl14的基质。我们发现这些周细胞直接来自早期发育过程中看到的动脉壁细胞。这些数据有助于澄清肾间质祖细胞复杂谱系关系的一小部分及其对肾血管相关壁细胞的贡献。

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引用次数: 0

Direct activation of folate receptor 4 by thyroid hormone suggests its role in the development of adult intestinal epithelium during Xenopus laevis metamorphosis 叶酸受体4被甲状腺激素直接激活，提示其在非洲爪蟾变态成虫肠上皮发育过程中起重要作用。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-12 DOI: 10.1016/j.ydbio.2025.11.006

Kenta Fujimoto , Yuki Shibata , Morihiro Okada , Yun-Bo Shi , Takashi Hasebe

Amphibian metamorphosis is tightly regulated by thyroid hormone (TH). During this process, most larval epithelial cells in the Xenopus laevis intestine undergo apoptosis, whereas a small population dedifferentiates into adult epithelial stem cells. They subsequently proliferate and differentiate to form a trough-crest epithelial architecture similar to the mammalian crypt-villus axis. We have previously identified a number of TH-responsive genes likely involved in this intestinal remodeling. Here, we focus on one such gene, folate receptor 4 (folr4). We examined the spatiotemporal expression of folr4.L by using quantitative RT-PCR and in situ hybridization chain reaction (HCR) and found that folr4.L expression is highly upregulated during both natural and TH-induced metamorphosis. Interestingly, in the epithelium at the climax of metamorphosis, folr4.L is specifically expressed in the proliferating and/or differentiating adult epithelial cells located adjacent to proliferating adult stem cells, which express intestinal stem cell marker leucine-rich repeat-containing G protein-coupled 5 (lgr5). Moreover, we identified a TH response element (TRE) in the folr4.L promoter that binds to the heterodimer of TH receptor (TR) and 9-cis retinoic acid receptor (RXR) in vitro and mediates T3-dependent transcriptional activation in vivo. Phylogenetic analysis suggested that X. laevis Folr4.L may be more closely related to riboflavin binding protein (Rfbp) than mammalian FOLR4. These findings suggest that TH-induced Folr4.L might be involved in the development of adult intestinal epithelium.

两栖动物的变态受甲状腺激素（TH）的严格调控。在这一过程中，非洲爪蟾肠道的大多数幼虫上皮细胞发生凋亡，而一小部分分化为成体上皮干细胞。它们随后增殖并分化形成类似于哺乳动物隐窝绒毛轴的谷嵴上皮结构。我们之前已经确定了一些th反应基因可能参与这种肠道重塑。在这里，我们集中在一个这样的基因，叶酸受体4 （folr4）。我们检测了folr4的时空表达。L采用定量RT-PCR和原位杂交链反应（HCR），发现folr4。L的表达在自然和th诱导的变态过程中都高度上调。有趣的是，在上皮变态的顶点，folr4。L在增殖和/或分化成体上皮细胞中特异性表达，这些细胞位于增殖成体干细胞附近，表达肠道干细胞标记物富含亮氨酸的重复- G蛋白偶联5 （lgr5）。此外，我们在folr4中发现了TH响应元件（TRE）。L启动子，在体外结合TH受体（TR）和9-顺式维甲酸受体（RXR）异二聚体，并在体内介导t3依赖性转录激活。系统发育分析表明，X. laevis Folr4。L可能比哺乳动物的FOLR4与核黄素结合蛋白（Rfbp）关系更密切。这些发现提示th诱导的Folr4。L可能参与了成人肠上皮的发育。

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引用次数: 0

Discovering the unexpected: Insights into the dynamics of mouse neural tube closure revealed by time-lapse imaging 发现意想不到的：延时成像揭示的小鼠神经管闭合动力学的见解。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-10 DOI: 10.1016/j.ydbio.2025.11.002

Claire Marie Moran , Irene E. Zohn

The use of time-lapse imaging to study neural tube closure in mouse embryos has provided unexpected insights into the complex morphogenetic processes involved. When neural tube closure is disrupted, it leads to neural tube defects (NTDs), which are among the most common structural birth defects in humans, associated with long-term disabilities and death. This review explores the growing body of research on time-lapse imaging experiments conducted in mice, emphasizing discoveries of the dynamic cellular movements and changes that enable neural tube formation. Advances in mouse embryo culture and live imaging techniques have enabled visualization of dynamic cellular movements and shape changes during neural tube formation, allowing researchers to observe abnormal cell behaviors in genetic mouse models with neural tube closure defects. These studies use transgenic reporters, conditional mouse genetics, and various physical and pharmacological interventions to track tissue and cell behavior and elucidate the underlying molecular and biophysical mechanisms as neural folds rise and fuse at the dorsal midline. Observing neural tube closure in real time has led to important findings, including revealing the crucial role of the surface ectoderm in supporting neural fold elevation and fusion. The coordination of apical constriction with cell cycle progression and apoptosis helps shape the neural plate. Analyzing convergent extension shows that oriented neighbor exchanges—requiring planar cell polarity signaling—drive polarized protrusive activity and actomyosin contractility, along with coordinated apical constriction to elevate and bring the neural folds together. Future innovations are expected to improve the measurement of biomechanical forces during neural tube formation and visualization of deep tissues to clarify mechanisms of cranial mesenchyme morphogenesis during cranial neural fold elevation.

利用延时成像技术研究小鼠胚胎中的神经管闭合，为涉及的复杂形态发生过程提供了意想不到的见解。当神经管闭合被破坏时，它会导致神经管缺陷（NTDs），这是人类最常见的结构性出生缺陷之一，与长期残疾和死亡有关。这篇综述探讨了在小鼠中进行的延时成像实验的研究，强调了动态细胞运动和使神经管形成的变化的发现。小鼠胚胎培养和实时成像技术的进步，使研究人员能够在神经管形成过程中可视化细胞的动态运动和形状变化，从而观察具有神经管闭合缺陷的遗传小鼠模型中的异常细胞行为。这些研究使用转基因报告者、条件小鼠遗传学和各种物理和药理学干预来跟踪组织和细胞行为，并阐明神经褶皱在背中线上升和融合的潜在分子和生物物理机制。实时观察神经管闭合导致了重要的发现，包括揭示了表面外胚层在支持神经褶皱提升和融合中的关键作用。神经板顶端收缩与细胞周期进程和细胞凋亡的协调有助于形成神经板。收敛性伸展分析表明，定向相邻交换（需要平面细胞极性信号传导）驱动极化突起活动和肌动球蛋白收缩，以及协调的顶端收缩，以提升和聚集神经褶皱。未来的创新有望改善神经管形成过程中生物力学力的测量和深部组织的可视化，以阐明颅神经褶皱提升过程中颅间质形态发生的机制。

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引用次数: 0

A zebrafish rbm24a-GFP knock-in line for monitoring lineage-specific dynamic protein expression and function 用于监测谱系特异性动态蛋白表达和功能的斑马鱼rbm24a-GFP敲入线。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-08 DOI: 10.1016/j.ydbio.2025.11.001

Ziwei Ying , Yizhuang Zhang , Audrey Saquet , Ming Shao , De-Li Shi , Raphaëlle Grifone

The RNA-binding protein Rbm24 is evolutionarily conserved, and its coding gene displays tissue-specific expression in vertebrates. However, the dynamic localization of this protein in different cell lineages remains elusive. We have generated a zebrafish rbm24a-GFP knock-in line in which endogenous Rbm24a is tagged with GFP, allowing the precise monitoring and systematic characterization of its spatiotemporal expression and subcellular localization during development and in the adult. Rbm24a-GFP not only shows strongly restricted expression in a subset of tissues, but also displays cell type- and stage-specific subcellular localization patterns. The protein mainly localizes in the cytoplasm of lens fiber cells and progenitors of sensory hair cells. It undergoes dynamic cytoplasm to nucleus translocation during differentiation of myoblasts and cardiomyoblasts. We further examined the effectiveness of this knock-in line for inhibiting Rbm24a function. Targeted degradation of Rbm24a-GFP using the zGrad system produces phenotypes of zygotic rbm24a mutants or morphants, with defective heart morphogenesis and disrupted cardiac muscle integrity. Therefore, this line will be particularly useful for understanding Rbm24a-GFP dynamic expression and localization changes under homeostasis and pathological conditions. It also enriches the resource of zebrafish knock-in line and provides a convenient tool for functional study of the protein through degron-mediated conditional degradation.

rna结合蛋白Rbm24具有进化保守性，其编码基因在脊椎动物中具有组织特异性表达。然而，该蛋白在不同细胞系中的动态定位仍然难以捉摸。我们已经生成了一个斑马鱼Rbm24a -GFP敲入系，其中内源性Rbm24a被GFP标记，允许在发育和成年期间对其时空表达和亚细胞定位进行精确监测和系统表征。Rbm24a-GFP不仅在组织亚群中表现出强烈的限制性表达，而且还表现出细胞类型和阶段特异性的亚细胞定位模式。该蛋白主要存在于晶状体纤维细胞的细胞质和感觉毛细胞的祖细胞中。在成肌细胞和心肌细胞分化过程中，它经历了细胞质向细胞核的动态移位。我们进一步研究了该敲入序列抑制Rbm24a功能的有效性。使用zGrad系统靶向降解rbm24a - gfp产生合子rbm24a突变体或变形体的表型，具有心脏形态发生缺陷和心肌完整性破坏。因此，这条细胞系对于了解Rbm24a-GFP在稳态和病理条件下的动态表达和定位变化特别有用。它丰富了斑马鱼敲入细胞系的资源，并通过降解介导的条件降解为研究该蛋白的功能提供了便利的工具。

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引用次数: 0

Nicotinic acetylcholine receptors function with adhesion molecule SAX-7 to reverse cell orientation during migration 烟碱乙酰胆碱受体与粘附分子SAX-7一起作用，在迁移过程中逆转细胞取向。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-06 DOI: 10.1016/j.ydbio.2025.10.010

Joana Antonio , Elizabeth Strang , Rom David L. Arca , Matthew H. Sazinsky , Sarah Hasel-Kolossa , Abigail Wiesenthal , Jose Francisco Carranza Celis , Trisha Gongalore , Sagun Bhandari , Sadia Yeasmin , Mihoko Kato

Cell migration is an important process underlying animal embryonic body patterning, organogenesis, and diseases like metastatic cancer. Acetylcholine (ACh) signaling plays a key role in the migration of various cell types and cancer cells, yet in vivo studies are lacking. We investigated the function of nicotinic ACh receptors (nAChRs) on the migration of a gonadal leader cell, the linker cell (LC). During C. elegans male gonadogenesis, the LC migrates posteriorly along the ventral body wall, following a path that runs parallel and adjacent to the ACh-releasing ventral nerve cord (VNC). Excess ACh reoriented the polarity of the LC from posterior-facing to anterior-facing through an intermediate stage of facing the ventral body wall. nAChRs, which are expressed by both the VNC and LC, were required for the LC reversal response. The specific combination of subunits of the pentameric nAChR produced different reversal responses, with acr-16(−) and lgc-9(−) mutants inhibiting and acr-15(−) promoting reversals. LC reversal in response to excess ACh also required the L1 cell adhesion molecule (L1CAM), SAX-7, which is expressed by both VNC and LC. We propose that an increase in ACh signaling in the VNC and LC promotes stronger SAX-7 mediated adhesion of the LC to the ventral body wall, causing the LC to change directions from posterior to ventral facing.

细胞迁移是动物胚胎体形成、器官发生和转移性癌症等疾病的重要过程。乙酰胆碱（Acetylcholine, ACh）信号在各种细胞类型和癌细胞的迁移中起着关键作用，但缺乏体内研究。我们研究了烟碱乙酰胆碱受体（nAChRs）对性腺领导细胞连接细胞（LC）迁移的作用。在秀丽隐杆线虫雄性性腺生成过程中，LC沿着腹侧体壁向后移动，沿着平行和邻近释放乙酰胆碱的腹侧神经索（VNC）的路径。过量的乙酰胆碱通过面向腹壁的中间阶段将LC的极性从面向后转向面向前。nachr由VNC和LC共同表达，是LC反转响应所必需的。五聚体nAChR亚基的特定组合产生不同的逆转反应，acr-16（-）和lgc-9（-）突变体抑制逆转，而acr-15（-）促进逆转。过量ACh的LC逆转还需要L1细胞粘附分子（L1CAM） SAX-7，该分子由VNC和LC共同表达。我们认为，VNC和LC中ACh信号的增加促进了SAX-7介导的LC与腹侧体壁的更强粘附，导致LC从后向腹侧改变方向。

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引用次数: 0

The Neural Tube CURE: Engaging undergraduate students in a relevant developmental biology research course. 神经管治疗：让本科生参与相关的发育生物学研究课程。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2025-11-01 Epub Date: 2025-07-28 DOI: 10.1016/j.ydbio.2025.07.010

Anneke Dixie Kakebeen, Joshua Y Fandel, Lee A Niswander

Research experience is necessary for undergraduate students who aim to become professional scientists; however, gaining research experience is a daunting task fraught with challenges often beyond a student's control. To create an opportunity for more undergraduate students to engage in relevant developmental biology research with meaningful societal impact, we devised a new course-based undergraduate research experience (CURE) focused on identifying candidate genes that may be required for human neural tube closure. In the CURE outlined here, students used molecular biology and cloning techniques to generate CRISPR knockouts of specific genes in chick embryos and measured subsequent neural tube defect frequency. Pre- and post-surveys from students provide evidence that after participating in the course, students made gains in self-confidence and science identity, met learning goals, and felt that all lectures and assignments were valuable. Students also reported that the course led them to realize the impact and importance of developmental biology research. To solidify the connection between the work that students do in the course and the world around them, we also propose a future activity to help students to engage more deeply with the societal context of neural tube defects. In this resource article, we present the Neural Tube CURE as a valuable course to engage students in novel developmental biology research.

研究经验是本科生成为专业科学家的必要条件；然而，获得研究经验是一项艰巨的任务，充满了学生无法控制的挑战。为了让更多的本科生有机会参与相关的发育生物学研究，并产生有意义的社会影响，我们设计了一个新的基于课程的本科生研究体验（CURE），专注于识别人类神经管闭合可能需要的候选基因。在这里概述的CURE中，学生们使用分子生物学和克隆技术在鸡胚胎中产生CRISPR敲除特定基因，并测量随后神经管缺陷的频率。学生参与课程前后的调查表明，学生在自信和科学认同方面有所提高，达到了学习目标，并且觉得所有的讲座和作业都是有价值的。学生们还报告说，这门课程使他们认识到发育生物学研究的影响和重要性。为了巩固学生在课程中所做的工作与他们周围的世界之间的联系，我们还提出了一个未来的活动，以帮助学生更深入地参与神经管缺陷的社会背景。在这篇资源文章中，我们将神经管治疗作为一门有价值的课程来吸引学生进行新的发育生物学研究。

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引用次数: 0