Developmental biology最新文献_第5页

PRDM paralogs are required for Meckel's cartilage formation during mandibular bone development 在下颌骨发育过程中，梅克尔软骨的形成需要PRDM类似物。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.ydbio.2025.12.002

Qootsvenma Denipah-Cook , Bryanna V. Saxton , Kristin B. Artinger , Lomeli C. Shull

Mandibular bone development depends on the formation of a cartilaginous anlage Meckel's cartilage derived from neural crest cells (NCC) and intramembranous ossification or direct differentiation of NCCs toward osteoblasts. Wnt/β-catenin signaling drives osteogenic vs chondrogenic differentiation and must be tightly controlled during the differentiation of osteochondroprogenitors. Chromatin remodelers add hierarchal regulation to the activation and repression of crucially timed gene regulatory networks and signaling cascades. In this study, we investigated the function of two chromatin remodelers—histone methyltransferases, PRDM3 and PRDM16 during murine craniofacial development. Conditionally ablating both Prdm3 and Prdm16 in the neural crest lineage using the Wnt1-Cre driver resulted in dramatic craniofacial phenotypes, including a severely hypoplastic mandible with complete absence of Meckel's cartilage at E18.5. Focusing on the Meckel's cartilage and mandibular bone phenotype, histological analysis demonstrated a significant increase in RUNX2+ osteoblast precursors, and loss of SOX9+ chondrogenic cells, suggesting an increase in osteoblast progenitors at the expense of chondrocytes that would otherwise form the Meckel's cartilage. This was not due to alterations in proliferation or apoptosis, as we observed no significant changes in the number of phosphoH3+ or cleaved caspase3+ cells in the mandibular process at E11.5, suggesting lack of NCC-derived chondrocytes is due to a change in NCC osteochondroprogenitor fate decisions. mRNA transcripts and protein abundance of Wnt/β-catenin signaling components were elevated in the mandibular process during initial NCC osteochondroprogenitor condensation events, suggesting PRDM3 and PRDM16 normally restrict expression of Wnt/β-catenin signaling components during NCC-derived osteochondroprogenitor differentiation to promote chondrogenesis and Meckel's cartilage formation. Taken together, PRDM3 and PRDM16 are required for NCC differentiation toward chondrocytes during Meckel's cartilage formation by controlling proper spatiotemporal Wnt/β-catenin transcriptional activity and this process is necessary for morphogenesis of the developing mandible.

下颌骨的发育依赖于神经嵴细胞（NCC）衍生的软骨基质梅克尔软骨的形成和膜内骨化或NCC向成骨细胞的直接分化。Wnt/β-catenin信号驱动成骨与软骨分化，在骨软骨祖细胞分化过程中必须受到严格控制。染色质重塑者为激活和抑制关键时间基因调控网络和信号级联增加了层次调节。在这项研究中，我们研究了两种染色质重塑酶-组蛋白甲基转移酶PRDM3和PRDM16在小鼠颅面发育中的功能。使用Wnt1-Cre驱动器有条件地消融神经嵴谱系中的Prdm3和Prdm16导致显著的颅面表型，包括E18.5时严重发育不良的下颌骨和完全缺失的Meckel软骨。关注Meckel软骨和下颌骨表型，组织学分析显示RUNX2+成骨细胞前体显著增加，SOX9+软骨细胞缺失，提示成骨细胞前体增加，以牺牲形成Meckel软骨的软骨细胞为代价。这不是由于增殖或凋亡的改变，因为我们观察到E11.5时下颌突中phosphoH3+或cleaved caspase3+细胞的数量没有显著变化，这表明缺乏NCC来源的软骨细胞是由于NCC骨软骨祖细胞命运决定的改变。在NCC初始骨软骨祖细胞凝聚过程中，下颌过程中Wnt/β-catenin信号组分的mRNA转录物和蛋白丰度升高，提示在NCC源性骨软骨祖细胞分化过程中，PRDM3和PRDM16通常限制Wnt/β-catenin信号组分的表达，以促进软骨形成和Meckel软骨形成。综上所述，PRDM3和PRDM16是Meckel软骨形成过程中NCC向软骨细胞分化所必需的，通过控制适当的时空Wnt/β-catenin转录活性，这一过程是发育中的下颌骨形态发生所必需的。

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引用次数: 0

Genetic background influences the extent and severity of cilia-related congenital anomalies in Ift56/Ttc26 mutant mice 遗传背景影响Ift56/Ttc26突变小鼠纤毛相关先天性异常的程度和严重程度。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-12-05 DOI: 10.1016/j.ydbio.2025.12.003

Daisy Xin , Mycah Sewell , Elli Emmanouil , Scott D. Weatherbee

Multiple congenital anomalies have been linked to defects in the formation or function of a small cellular organelle called the cilium. The severity of cilia-related syndromes (ciliopathies) ranges from viable with fertility defects to embryonic lethal, often with different mutations in the same gene resulting in highly variable phenotypes. While some of the disparity is likely due to differential effects of specific mutations, genetic variants at other loci could serve as ciliopathy modifiers. This could lead to the same mutation causing distinct effects in different individuals. Here, we show that a loss-of-function mutation in Ift56, a key gene involved in cilia protein trafficking, has dramatic phenotypic differences depending on the genetic background in mice. It has previously been reported that in the Balb/cByJ background, Ift56^hop homozygous mutants are viable as adults, males are sterile, and homozygotes move their hindlimbs in tandem, resulting in a hopping gait. In contrast, we demonstrate that in the C57BL/6J background, Ift56^hop homozygotes are perinatal lethal, and have multiple skeletal and organ defects, including the formation of tracheoesophageal fistulas. Using Single Nucleotide Polymorphisms (SNPs) that differ between these mouse strains, we show that a modifier of the Ift56^hop phenotype maps to Chromosome 4. Mutations in IFT56 and other cilia-related genes are being discovered in a growing number of human patients so understanding the mechanisms of their pathology is critical. Our study highlights the use of mouse models to identify ciliopathy modifier loci, with direct implications for human diagnostics.

多种先天性异常与一种叫做纤毛的小细胞器的形成或功能缺陷有关。纤毛相关综合征（纤毛病）的严重程度从具有生育缺陷的可存活性到胚胎致死性不等，通常在同一基因中具有不同的突变，导致表型高度可变。虽然某些差异可能是由于特定突变的不同影响，但其他位点的遗传变异可能作为纤毛病的修饰因子。这可能导致相同的突变对不同的个体产生不同的影响。在这里，我们发现Ift56（一个参与纤毛蛋白运输的关键基因）的功能缺失突变在小鼠中具有显著的表型差异，这取决于遗传背景。先前有报道称，在Balb/cByJ背景下，Ift56hop纯合突变体在成年后存活，雄性不育，纯合子移动后肢，导致跳跃步态。相反，我们证明在C57BL/6J背景下，Ift56hop纯合子是围产期致命的，并且具有多种骨骼和器官缺陷，包括气管食管瘘的形成。利用这些小鼠品系之间不同的单核苷酸多态性（snp），我们发现Ift56hop表型的修饰子映射到4号染色体。在越来越多的人类患者中发现了IFT56和其他纤毛相关基因的突变，因此了解其病理机制至关重要。我们的研究强调了使用小鼠模型来识别纤毛病修饰位点，这对人类诊断具有直接意义。

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引用次数: 0

Stay or stray: Lpar1 regulates neutrophil retention and epidermal homeostasis in early zebrafish development 停留或游离：Lpar1调节斑马鱼早期发育中的中性粒细胞滞留和表皮稳态。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-12-08 DOI: 10.1016/j.ydbio.2025.12.005

Shih-Chi Li , Yu-Chi Lin , Chung-Der Hsiao , Shyh-Jye Lee

Neutrophils play essential roles in host defense, but the mechanisms governing their developmental distribution remain poorly understood. Here, we identify a previously unrecognized function of lysophosphatidic acid receptor 1 (Lpar1) in maintaining neutrophil retention during early zebrafish development. Contrary to its previously described pro-inflammatory role, Lpar1 acts in an anti-inflammatory manner by preventing premature neutrophil dispersal. Mechanistically, Lpar1 regulates the expression of cxcl12a in the caudal hematopoietic tissue (CHT), establishing a novel Lpar1–Cxcl12a signaling axis that governs neutrophil localization. Lpar1 also influences neutrophil mobility through its effects on vascular integrity in the CHT, which is severely disrupted in Lpar1 morphants but may be mildly affected in Lpar1 mutants. Dispersed neutrophils are predominantly recruited to the superficial epidermal layer, where numerous apoptotic cells are present. Collectively, these findings refine current models of immune regulation during development and reveal an alternative mechanism that may contribute to the development of inflammatory skin disorders.

中性粒细胞在宿主防御中发挥着重要作用，但其发育分布的机制尚不清楚。在这里，我们发现了一种以前未被认识到的溶血磷脂酸受体1 （Lpar1）在维持斑马鱼早期发育过程中的中性粒细胞保留中的功能。与先前描述的促炎作用相反，Lpar1通过防止中性粒细胞过早分散而起到抗炎作用。从机制上讲，Lpar1调节尾侧造血组织（CHT）中cxcl12a的表达，建立了一个新的Lpar1- cxcl12a信号轴，控制中性粒细胞定位。Lpar1还通过其对CHT血管完整性的影响影响中性粒细胞的流动性，在Lpar1突变体中血管完整性受到严重破坏，但在Lpar1突变体中可能受到轻微影响。分散的中性粒细胞主要聚集到表皮浅层，那里存在大量凋亡细胞。总的来说，这些发现完善了目前发育过程中免疫调节的模型，并揭示了可能导致炎症性皮肤疾病发展的另一种机制。

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引用次数: 0

Electroporation-based gene delivery and whole-organoid imaging in human retinal organoids 基于电穿孔的基因传递和人类视网膜类器官的全器官成像。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.ydbio.2025.11.016

Keevon Flohr , Michael Janeček , Lingyun Wang , Vicente Valle , Shaohua Pi , Rui T. Peixoto , Susana da Silva

Human retinal organoids (hRetOrg) derived from human induced pluripotent stem cells (hiPSCs) have emerged as powerful in vitro systems for studying retinal development, modeling retinal diseases, and evaluating therapeutic strategies. However, current genetic manipulation approaches, such as stable hiPSC line generation and viral transduction, are laborious and costly, offering limited spatial specificity and high variability in transgene expression. Here, we report a rapid, scalable, and spatially precise electroporation-based platform for efficient plasmid-based gene delivery in early-stage hRetOrg. Our method enables tunable and region-specific transfection of retinal progenitor cells without viral vectors or clonal selection. When coupled with resonant-scanning two-photon microscopy, this approach allows fast live cell imaging of whole organoids with subcellular resolution. Taken together, our versatile system supports high-throughput genetic manipulation and imaging in intact hRetOrg, advancing studies of human retinal development, gene function, and disease pathophysiology.

来源于人诱导多能干细胞（hiPSCs）的人类视网膜类器官（hregg）已成为研究视网膜发育、视网膜疾病建模和评估治疗策略的强大体外系统。然而，目前的基因操作方法，如稳定的hiPSC细胞系生成和病毒转导，是费力和昂贵的，在转基因表达中提供有限的空间特异性和高可变性。在这里，我们报告了一个快速、可扩展、空间精确的基于电穿孔的平台，用于早期hreg中高效的基于质粒的基因传递。我们的方法使视网膜祖细胞的可调和区域特异性转染无需病毒载体或克隆选择。当与共振扫描双光子显微镜相结合时，这种方法可以对整个类器官进行亚细胞分辨率的快速活细胞成像。综上所述，我们的多功能系统支持完整hreg的高通量遗传操作和成像，推进人类视网膜发育、基因功能和疾病病理生理学的研究。

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引用次数: 0

Axial rotation comprises concurrent twisting and bending as distinct morphogenetic components in Ciona 轴向旋转包括同时发生的扭曲和弯曲，这是Ciona中不同的形态发生成分。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI: 10.1016/j.ydbio.2025.12.008

Yuki S. Kogure , Satoru Okuda , Kotaro Oka , Kohji Hotta

Axial rotation (AR), a morphogenetic movement that reshapes the body axis, is widely observed in chordates, including mice and rats. AR involves complex three-dimensional deformations; however, its geometric characteristics and regulatory mechanisms remain poorly understood. Here, using the chordate Ciona robusta (Ciona intestinalis type A), we demonstrate that AR consists of two differentially regulated components—leftward bending and clockwise twisting along the anterior–posterior axis. A comparison between chorionated and dechorionated embryos revealed that dechorionation randomized the bending direction, while twisting remained consistently clockwise. Inhibition of TGF-β signaling with SB431542 randomized both deformations. Quantitative analysis of twisting angles indicated uniform clockwise twisting along the axis, peaking during the tailbud stage and proceeding in the tail region, independent of the tip, trunk, or myofibril patterning. Although overall twisting was reduced under TGF-β inhibition, the tail exhibited disorganized twisting. The sum of absolute twisting-angle differences in every 10 μm remained comparable to the wild type (WT). This suggests that twisting is intrinsically generated, while TGF-β signaling aligns local twisting into a coordinated global direction. Our findings dissected the mechanisms of AR in Ciona and highlight the multilayered regulation underlying the morphogenesis of the chordate body plan and providing a foundation for understanding its biomechanical and molecular bases.

轴向旋转（AR）是一种重塑身体轴的形态发生运动，在脊索动物中广泛观察到，包括小鼠和大鼠。AR涉及复杂的三维变形；然而，其几何特征和调控机制仍然知之甚少。在这里，我们使用脊索动物robusta (chiona nestiinalis type A)，证明AR由两个不同调节的成分组成——沿前后轴向左弯曲和顺时针扭曲。绒毛膜剥离胚胎与去绒毛膜剥离胚胎的比较表明，去绒毛膜剥离胚胎的弯曲方向随机化，而扭曲方向始终保持顺时针方向。SB431542对TGF-β信号的抑制随机化了这两种变形。扭曲角度的定量分析表明，沿轴线均匀顺时针扭曲，在尾芽阶段达到峰值，并在尾部区域进行，与尖端、躯干或肌原纤维的模式无关。虽然在TGF-β抑制作用下，整体扭曲减少，但尾部扭曲呈现无组织。每10 μm的绝对扭转角差之和与野生型（WT）相当。这表明扭曲是内在产生的，而TGF-β信号将局部扭曲对齐到协调的全局方向。我们的研究结果剖析了AR在Ciona中的机制，并强调了脊索动物体表形态发生的多层调控，为理解其生物力学和分子基础提供了基础。

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引用次数: 0

Targeting the melanocytes of the inner ear: A comparison of different CreER lines 针对内耳黑色素细胞：不同CreER系的比较。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-12-13 DOI: 10.1016/j.ydbio.2025.12.009

Mahesh K. Nayak , Miaomiao Du , Rene Vielman Quevedo , Kristina Ly , Celia R. Bloom , Martín L. Basch , Justine Renauld

The inner ear is responsible for hearing and balance. During development, the inner ear undergoes extensive morphogenesis to create a coil shaped cochlea and three semicircular canals from an original flat otic placode. During this morphogenesis, neural crest cells migrate into the inner ear in formation to become either glial cells or melanocytes. The glial cells are located in the cochleo-vestibular ganglion and the melanocytes reside in the stria vascularis in the cochlea and dark cells zone in the vestibule. The stria vascularis pumps potassium ions into the scala media, generating a positive endocochlear potential which is crucial to the mechanosensory cells for auditory signal transduction. Any defect in strial cells leads to the dysregulation of ionic composition of the endolymph, ultimately resulting in deafness. Despite this, we still do not know exactly how the stria vascularis develops and functions.

To date, there is an absence of Cre driver mouse lines that effectively facilitate the study of individual cell development and functions within the stria vascularis, limiting our ability to understand strial deafness. Furthermore, the use of CreER transgenic mice lines introduces the possibility of poor recombination and non-specific expression. Therefore, it is necessary to establish a mouse line targeting each cell type within the stria vascularis.

The present study aims to determine the most appropriate CreER transgenic line targeting the melanocytes of the inner ear by comparing three CreER mouse lines related to melanocyte development: Pax3, Dct, and Tyr. The CreER mice were crossed with tdTomato reporter mice and induced with tamoxifen at three time points E11.5, P0, and P28 to study the spatiotemporal recombination in the inner ear. We quantify the recombination efficiency in the intermediate cells at each time point and identify important variations in both efficiency and specificity for the three lines. This study focusing on cochlear and vestibular melanocytes provides a much-needed tool to study melanocyte development and function in the inner ear with spatiotemporal control.

内耳负责听力和平衡。在发育过程中，内耳经历了广泛的形态发生，形成了线圈状的耳蜗和三个半规管。在这种形态发生过程中，神经嵴细胞迁移到内耳形成胶质细胞或黑素细胞。胶质细胞位于耳蜗-前庭神经节，黑素细胞位于耳蜗的血管纹和前庭的暗细胞区。血管纹将钾离子泵入肌膜介质，产生正耳蜗电位，这对机械感觉细胞的听觉信号传导至关重要。审状细胞的任何缺陷都会导致内淋巴离子组成的失调，最终导致耳聋。尽管如此，我们仍然不知道血管纹是如何发育和发挥功能的。迄今为止，缺乏有效促进血管纹内单个细胞发育和功能研究的Cre驱动小鼠系，限制了我们理解审讯性耳聋的能力。此外，使用CreER转基因小鼠系引入了重组不良和非特异性表达的可能性。因此，有必要建立针对血管纹内每种细胞类型的小鼠细胞系。本研究旨在通过比较与黑素细胞发育相关的三种CreER小鼠系Pax3、Dct和Tyr，确定最合适的针对内耳黑素细胞的CreER转基因系。将CreER小鼠与tdTomato报告小鼠杂交，在E11.5、P0、P28三个时间点用他莫昔芬诱导，研究其内耳时空重组情况。我们量化了每个时间点中间细胞的重组效率，并确定了三种细胞系在效率和特异性方面的重要变化。这项以耳蜗和前庭黑素细胞为研究对象的研究为研究内耳黑素细胞的发育和功能提供了一个非常必要的工具。

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引用次数: 0

The RhoA signaling pathway is required for planarian intestinal regeneration RhoA信号通路是涡虫肠道再生所必需的。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-12-18 DOI: 10.1016/j.ydbio.2025.12.010

Runqiu Han , Ning Ding , Shuqi Li, Wei Liu, Yankai Liu, Qingnan Tian

Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. For most tissues and organs, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Planarians are able to regenerate any missing part of their body after injury, and are thus ideally suited for investigating organ regeneration. Here, we show that Rap1/RhoA/Cofilin pathway is responsible for the intestinal and neural regeneration in planarians. We found that Rap1 is enriched in planarian eyes and intestinal tissues. Both Rap1(RNAi) and RhoA(RNAi) animal commence with decreased expression of gut-specific progenitor marker. Meanwhile, knockdown of Cofilin, which co-expressed with RhoA, caused similar phenotypes with RhoA(RNAi). Moreover, we identified Rnd as a negative regulator of RhoA, the silencing of which recover the defects observed in RhoA(RNAi) animals. Therefore, our findings indicate that Rap1/RhoA/Cofilin pathway is an important regulator of the intestinal regeneration.

虽然有些动物能够再生器官，但实现这一目标的机制尚不清楚。对于大多数组织和器官，干细胞分化的时空动态和损伤前存在的组织的命运尚未被系统地表征。涡虫能够在受伤后再生身体的任何缺失部分，因此非常适合研究器官再生。在这里，我们发现Rap1/RhoA/Cofilin通路负责涡虫肠道和神经再生。我们发现Rap1在涡虫的眼睛和肠道组织中富集。Rap1（RNAi）和RhoA（RNAi）动物均以肠道特异性祖细胞标志物表达降低开始。同时，敲低与RhoA共表达的Cofilin，引起与RhoA（RNAi）相似的表型。此外，我们发现Rnd是RhoA的负调节因子，其沉默可以恢复在RhoA（RNAi）动物中观察到的缺陷。因此，我们的研究结果表明Rap1/RhoA/Cofilin通路是肠道再生的重要调节因子。

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引用次数: 0

Editorial: “Oogenesis: following the pattern and eccentricities” 社论：“卵子发生：遵循模式和怪癖”。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-12-19 DOI: 10.1016/j.ydbio.2025.12.012

Malgorzata Kloc PhD, Dr. Sc.

引用次数: 0

Plant-mediated synthesis of biocompatible Fe3O4 nanoparticles for magnetic hyperthermia therapy: A preclinical study in pharmaceutical nanotechnology 植物介导合成用于磁热疗法的生物相容性Fe3O4纳米颗粒：药物纳米技术的临床前研究。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-11-18 DOI: 10.1016/j.ydbio.2025.11.009

A.B. Pandhare , S.V. Mulik , A.S. Patil , D. Sohn , N.B. Birajdar , V.M. Khot , Moonis Ali Khan , A. Manikandan , Lalitha Gnanasekaran , D.S. Vijayan , S. Santhoshkumar , B.E. Keshta , S.D. Delekar , R.P. Patil

This study employs an eco-friendly approach to synthesize superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIO) using Aegle Marmelos (A. Marmelos) pulp extract as a surfactant as well as a reducing agent. The pulp extract from A. marmelos is medicinally employed to treat cholera, diabetes, skin infections, earaches, blood purification, and heart problems. Further, the XRD and TEM analyses confirmed the formation of SPIO nanoparticles with a cubic structure and crystallite sizes ranging from 5 to 12 nm. The FE-SEM showed that the SPIO displayed a uniform distribution with quasi-spherical morphology. FTIR evaluation directed the existence of iron-oxygen (Fe-O) bonds, while XPS analysis confirmed iron (Fe) in both +3 and + 2 oxidation states. SQUID studies verify the superparamagnetic nature of the material, with a magnetization (Ms) of 42.02 emu/g. Following characterization, the hyperthermia performance and specific loss power (SLP) of SPIO nanoparticles were systematically explored to assess their dependency on concentration, frequency, and the alternating magnetic field (AC field). These SPIO nanoparticles exhibit excellent hyperthermia proficiency (42–45 °C), with SLP values of 153.48 and 40.33 W/g at concentrations of 1 mg/mL in aqueous media (DI H₂O) and ethylene glycol media (E.G.), respectively, under an AC field (400 A). Furthermore, different concentrations of SPIO were tested for acute toxicity using a static renewal bioassay method. The results indicate non-toxic behavior towards vital organs such as the ovaries, gills, liver, heart, kidneys, brain, and muscles of the benthopelagic fish Cirrhinusmrigala. These findings highlight the potential of the SPIO nanoparticles as biocompatible for magnetic hyperthermia applications (MHT). These newly developed SPIO nanoparticles are suitable for deployment in the medical field, as they exhibit remarkable performance in the treatment of MHT when exposed to an AC field.

本研究采用生态友好的方法合成超顺磁性氧化铁（Fe3O4）纳米颗粒（SPIO），使用鹿茸（a . Marmelos）果肉提取物作为表面活性剂和还原剂。柑橘果肉提取物可用于治疗霍乱、糖尿病、皮肤感染、耳痛、血液净化和心脏问题。此外，XRD和TEM分析证实了SPIO纳米颗粒的形成，具有立方结构，晶粒尺寸在5 ~ 12 nm之间。FE-SEM分析表明，SPIO呈准球形均匀分布。FTIR评价表明铁-氧（Fe- o）键的存在，而XPS分析证实了铁（Fe）在+3和+2氧化态。SQUID研究证实了材料的超顺磁性，磁化强度（Ms）为42.02 emu/g。在表征之后，系统地探索了SPIO纳米颗粒的热疗性能和比损失功率（SLP），以评估它们对浓度、频率和交变磁场（AC field）的依赖性。这些SPIO纳米颗粒表现出优异的热疗能力（42-45℃），在交流电场（400 A）下，在水介质（DI H2O）和乙二醇介质（E.G.）中，浓度为1 mg/mL时，SLP值分别为153.48和40.33 W/g。此外，使用静态更新生物测定法测试了不同浓度的SPIO的急性毒性。结果表明，对底栖鱼的卵巢、鳃、肝脏、心脏、肾脏、大脑和肌肉等重要器官无毒。这些发现突出了SPIO纳米颗粒在磁热疗应用（MHT）方面具有生物相容性的潜力。这些新开发的SPIO纳米颗粒适合应用于医疗领域，因为它们在暴露于交流电场时表现出显著的治疗MHT的性能。

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引用次数: 0

Zebrafish pou3f3b controls saccular/auditory development and marks non-neuronal cells that delaminate from the otic vesicle to promote neuroblast maturation 斑马鱼的pou3f3b控制着囊状/听觉的发育，并标志着非神经元细胞从耳囊中剥离，以促进神经母细胞成熟。

IF 2.1 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology

Pub Date : 2026-02-01 Epub Date: 2025-11-17 DOI: 10.1016/j.ydbio.2025.11.010

Sydney E. Christensen , Maria Ali , Jorden N. Holland, Bruce B. Riley

The zebrafish otic vesicle initially develops with only two sensory maculae, each with distinct functions. The anterior utricular macula is indispensable for vestibular function, while the posterior saccular macula is the primary auditory endorgan in zebrafish. The unique identities of these maculae are specified in the early otic vesicle by differing levels of Fgf vs. Shh signaling, but few downstream effectors have been identified. pou3f3b is the only saccule-specific marker known, but its function has not been established. We generated a knockout allele of pou3f3b and found that it causes a persistent delay in accumulation of saccular hair cells due to a failure to activate saccular expression of fgf3. In addition, saccular hair cells exhibit reduced expression of Otoferlin caused by ectopic expression of neurog1. Defects in saccular hair cell development are fully rescued by misexpressing fgf3 or knocking down neurog1. Misexpression of pou3f3b causes loss of utricular pax5 expression and further truncates neurog1 in the posterior otic vesicle but does not otherwise alter macular development. In addition to regulating saccular development, pou3f3b is also expressed in a previously undescribed population of non-neuronal cells that delaminate from the otic vesicle and migrate together with developing neuroblasts to promote their maturation. Mutant neuroblasts show a marked delay in activation of expression of neurod1, causing a transient delay in accumulation of mature SAG neurons. Thus pou3f3b is required for timely development of SAG neurons and saccular/auditory hair cells.

斑马鱼耳囊最初只有两个感觉斑疹，每个感觉斑疹都有不同的功能。斑马鱼前庭功能不可缺少的是前庭黄斑前部，而后庭黄斑后部是主要的听觉内器官。这些斑疹的独特身份在早期耳小泡中通过不同水平的Fgf和Shh信号来指定，但很少有下游效应物被确定。Pou3f3b是唯一已知的红斑特异性标记，但其功能尚未确定。我们产生了pou3f3b的敲除等位基因，并发现由于无法激活fgf3的囊状表达，它会导致囊状毛细胞积累的持续延迟。此外，神经g1异位表达导致囊毛细胞Otoferlin表达降低。囊状毛细胞发育缺陷可通过错误表达fgf3或敲除neurog1来完全修复。pou3f3b的错误表达导致细胞内pax5的表达缺失，并进一步截断耳后囊中的neurog1，但不会改变黄斑的发育。除了调节囊泡发育外，pou3f3b还在先前描述的非神经元细胞群中表达，这些非神经元细胞从耳小泡脱落，并与发育中的神经母细胞一起迁移，以促进其成熟。突变的神经母细胞表现出明显的延迟激活neurod1的表达，导致成熟的SAG神经元积累的短暂延迟。因此，SAG神经元和囊状/听觉毛细胞的及时发育需要pou3f3b。

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