Journal of cell science最新文献_第4页

Differential splice isoforms of mouse CDK2 play functionally redundant roles during mitotic and meiotic division. 小鼠CDK2的不同剪接异构体在有丝分裂和减数分裂中发挥功能冗余作用。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-22 DOI: 10.1242/jcs.264291

Nathan Palmer, Nisan Ece Kalem-Yapar, Hanna Hultén, Umur Keles, S Zakiah A Talib, Jin Rong Ow, Tommaso Tabaglio, Christine M F Goh, Li Na Zhao, Ernesto Guccione, Kui Liu, Philipp Kaldis

{"title":"Differential splice isoforms of mouse CDK2 play functionally redundant roles during mitotic and meiotic division.","authors":"Nathan Palmer, Nisan Ece Kalem-Yapar, Hanna Hultén, Umur Keles, S Zakiah A Talib, Jin Rong Ow, Tommaso Tabaglio, Christine M F Goh, Li Na Zhao, Ernesto Guccione, Kui Liu, Philipp Kaldis","doi":"10.1242/jcs.264291","DOIUrl":"https://doi.org/10.1242/jcs.264291","url":null,"abstract":"In most mammals, the cell cycle kinase; cyclin-dependent kinase 2 (CDK2) is expressed as two major isoforms due to alternative splicing. The shorter CDK2 isoform: CDK2S, is expressed constitutively during the cell cycle and can be detected in several tissues. In contrast, the longer isoform: CDK2L, shows preferential expression in meiotically dividing cells and upon S-phase entry in the mitotic cycle. Both CDK2L and CDK2S form heteromeric complexes with cyclins A2 and E1 in vitro. However, complexes comprised of each isoform differ considerably in their kinase activity towards known CDK substrates. It is currently unknown whether the long and short isoforms of CDK2 play functionally different roles in vivo during either mitotic and meiotic divisions as conventional knockout methodology deletes both of the isoforms. Therefore, we generated mice expressing only CDK2S or CDK2L and found that both CDK2L and CDK2S are sufficient to support both mitotic and meiotic division when expressed in the absence of the other. This data contributes to the explanation of the apparent tolerance of the evolutionary loss of CDK2L expression in humans.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113146","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

The superficial tufted and mitral cell output neurons of the mouse olfactory bulb have dual roles in insulin sensing. 小鼠嗅球的浅簇状和二尖瓣细胞输出神经元在胰岛素感知中具有双重作用。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-19 DOI: 10.1242/jcs.264088

Louis John Kolling, Saptarsi Mitra, Catherine Anne Marcinkiewcz, Debra Ann Fadool

{"title":"The superficial tufted and mitral cell output neurons of the mouse olfactory bulb have dual roles in insulin sensing.","authors":"Louis John Kolling, Saptarsi Mitra, Catherine Anne Marcinkiewcz, Debra Ann Fadool","doi":"10.1242/jcs.264088","DOIUrl":"10.1242/jcs.264088","url":null,"abstract":"The olfactory bulb (OB) contains multiple, parallel projection neurons to relay the nature of a stimulus. In a mouse ex vivo slice preparation, we used patch-clamp electrophysiology to measure intrinsic properties, excitability, action potential (AP) shape, voltage-activated conductances, and neuromodulation in the newly-categorized superficial tufted cells (sTCs) compared with those of mitral cells (MCs). We propose that a marked difference in voltage-dependent current represents distinct ion channel populations that affect the kinetics of action potentials, and evokes an increase in sTC firing frequency, albeit both types of projection neurons having similar AP spiking activity. Triple-colored immunofluorescence and RNA scope were used to detect co-localization of the Kv1.3 ion channel and the insulin receptor in sTCs, with ∼73% of sTCs expressing both. The sTCs were modulated by bath application of insulin - increasing AP firing frequency by 97%, attributable to an 8% decrease in the intraburst interval, and a reduction of the latency to first spike by 37%. We conclude that there may be a range of neuromodulators of sTCs that may alter excitability and fine-tune olfactory information processing or metabolic balance.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086351","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

RhoGEF2 overexpression induces cell competition dependent on Ptp10D, Crumbs, and the Hippo signaling pathway. RhoGEF2过表达诱导依赖Ptp10D、crumb和Hippo信号通路的细胞竞争。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-19 DOI: 10.1242/jcs.264377

Natasha Fahey-Lozano, Marta Portela, John E La Marca, Helena E Richardson

{"title":"RhoGEF2 overexpression induces cell competition dependent on Ptp10D, Crumbs, and the Hippo signaling pathway.","authors":"Natasha Fahey-Lozano, Marta Portela, John E La Marca, Helena E Richardson","doi":"10.1242/jcs.264377","DOIUrl":"https://doi.org/10.1242/jcs.264377","url":null,"abstract":"In Drosophila melanogaster larval epithelial tissues, cells containing mutations in the apico-basal polarity protein, Scrib, are eliminated by cell competition when surrounded by wild-type cells. In scrib mutant cells, signaling mediated by the receptor-type tyrosine phosphatase Ptp10D upon engagement with its ligand Sas in the surrounding wild-type cells triggers cell competition via EGFR-Ras pathway inhibition and JNK pathway activation, which induces apoptosis of the mutant cells. Here, we investigate whether overexpression of RhoGEF2 (RhoGEF2OE), which induces Rho signaling and affects actin cytoskeleton regulators, acts similarly to Scrib depletion in cell competition. We show that RhoGEF2OE cells are eliminated when surrounded by wild-type cells, and Ptp10D knockdown increases RhoGEF2OE clone growth. Mechanistically, in clones moderately overexpressing RhoGEF2OE, Ptp10D knockdown rescued cell elimination by reducing Hippo signaling. Additionally, mutations in the apical cell polarity protein, Crb, partially rescued the elimination of RhoGEF2OE clones. In this setting, in which RhoGEF2OE is highly overexpressed, JNK and Hippo signaling were elevated while EGFR-Ras signaling was reduced, and crb loss normalized these pathways. Thus, RhoGEF2OE leads to clone elimination dependent on Crb, Ptp10D, and Hippo signaling.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086219","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

Regulation of cell shape and mechanics by Rho GEF/GAP in a proliferative epithelial tissue. Rho GEF/GAP在增殖上皮组织中对细胞形状和力学的调控。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-18 DOI: 10.1242/jcs.264163

Emeline Durel, Nathalie Bécot, Mathieu Pinot, Laurent Chesneau, Thierry Pécot, Roland Le Borgne

{"title":"Regulation of cell shape and mechanics by Rho GEF/GAP in a proliferative epithelial tissue.","authors":"Emeline Durel, Nathalie Bécot, Mathieu Pinot, Laurent Chesneau, Thierry Pécot, Roland Le Borgne","doi":"10.1242/jcs.264163","DOIUrl":"https://doi.org/10.1242/jcs.264163","url":null,"abstract":"Epithelial cell shape results from the combination of intrinsic properties of the actomyosin cytoskeleton and extrinsic properties due to physical interactions with neighbouring cells, in particular at the adherens junctions. In the Drosophila epidermis, non-muscle myosin type II (MyoII) is a key force regulator for the control of cell shape. MyoII is activated by Rho GTPases, themselves activated by guanine nucleotide exchange factors (GEFs) and inhibited by GTPase activating proteins (GAPs). Here, we screened 28 Drosophila GAPs and 36 GEFs on the pupal notum to identify regulators of MyoII distribution and dynamics, epithelial cell shape and cytokinesis. Among the candidates identified, we show that PlexA, a transmembrane GAP regulates the shape of sensory organ precursors in a cell-autonomous manner, and that RhoGEF Cyst acts downstream of Crumbs and trimeric G proteins Gβ13F/Gγ1 to regulate junctional MyoII and adherens junctions remodelling during interphase and cytokinesis, in a non-cell autonomous manner. This study provides a comprehensive basis of GEFs and GAPs impacting epithelia homeostasis, and shed light on the mechanisms linking actomyosin contractility, cell shape regulation and cell junction dynamics.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080781","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

Allele-specific conformational rescue of KIF1A(T99M) by genetic suppressors in a C. elegans model of KIF1A-associated neurological disorder. 基因抑制因子在线虫KIF1A相关神经系统疾病模型中对KIF1A（T99M）等位基因特异性构象的拯救

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-18 DOI: 10.1242/jcs.264216

Zihan Chen, Yongping Chai, Zhengyang Guo, Xuanyu Fu, Wei Li, Jinxiang Zhang, Guangshuo Ou, Hui Wang

{"title":"Allele-specific conformational rescue of KIF1A(T99M) by genetic suppressors in a C. elegans model of KIF1A-associated neurological disorder.","authors":"Zihan Chen, Yongping Chai, Zhengyang Guo, Xuanyu Fu, Wei Li, Jinxiang Zhang, Guangshuo Ou, Hui Wang","doi":"10.1242/jcs.264216","DOIUrl":"https://doi.org/10.1242/jcs.264216","url":null,"abstract":"KIF1A-associated neurological disorder (KAND) arises from mutations in the microtubule motor KIF1A, disrupting synaptic vesicle transport. Here, we investigate the pathogenic T99M substitution in KIF1A's P-loop, which induces steric hindrance, impairing ATP/ADP coordination and motor activity. Using CRISPR-engineered C. elegans expressing the homologous UNC-104(T95M) mutation, we conducted forward genetic screens and identified recurrent intragenic suppressors (T95V/I) that restored animal motility and synaptic vesicle distribution. Molecular dynamics simulations revealed that replacing methionine with valine/isoleucine alleviated steric clashes in the nucleotide-binding pocket and stabilized Mg²⁺-ATP coordination. Biochemical assays showed that T95V/I partially recovered microtubule gliding velocity and processivity, demonstrating that even modest motor reactivation mitigates neuronal dysfunction. Inspired by prior success with fisetin in rescuing the KIF1A R11Q variant, we propose allele-specific conformational stabilization as a therapeutic strategy for KAND. Our findings highlight the structural plasticity of motor domain and provide a framework for precision therapies targeting pathogenic variants through genetic suppressors.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080770","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

Morphological reprogramming of primary cilia length mitigates the fibrotic phenotype in fibroblasts across diverse fibrotic conditions. 在不同的纤维化条件下，原纤毛长度的形态学重编程减轻了成纤维细胞的纤维化表型。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-17 DOI: 10.1242/jcs.264191

Priyanka Verma, Bharat Yalavarthi, Swati Bhattacharyya, Dinesh Khanna, Johann E Gudjonsson, Lam C Tsoi, Rebecca Wells, Rebecca L Ross, Natalia Riobo-Del Galdo, Francesco Del Galdo, Sean M Fortier, Maria E Teves, John Varga, Dibyendu Bhattacharyya

{"title":"Morphological reprogramming of primary cilia length mitigates the fibrotic phenotype in fibroblasts across diverse fibrotic conditions.","authors":"Priyanka Verma, Bharat Yalavarthi, Swati Bhattacharyya, Dinesh Khanna, Johann E Gudjonsson, Lam C Tsoi, Rebecca Wells, Rebecca L Ross, Natalia Riobo-Del Galdo, Francesco Del Galdo, Sean M Fortier, Maria E Teves, John Varga, Dibyendu Bhattacharyya","doi":"10.1242/jcs.264191","DOIUrl":"https://doi.org/10.1242/jcs.264191","url":null,"abstract":"Myofibroblast differentiation, shared across fibrotic diseases, is marked by actin polymerization and assembly of αsmooth muscle actin (αSMA) stress fibers. Primary cilia (PC) are solitary membrane-bound organelles present on the majority of cells. PC length regulation is a complex process influenced by actin polymerization. We discovered that fibroblasts from diverse fibrotic conditions display significantly reduced PC length ex vivo. Treatment of healthy fibroblasts with profibrotic TGF-β1 induced PC shortening, while silencing ACTA2 in systemic sclerosis (SSc) skin fibroblasts caused PC elongation. Importantly, we found that PC length was negatively correlated with αSMA levels in TGF-β1-treated healthy fibroblasts and pharmacologically dedifferentiated myofibroblasts. Our results suggest that during the fibrotic response, higher-order actin polymerization, along with microtubule destabilization by tubulin deacetylation, drives PC length shortening. In contrast, PC length elongation via stabilization of microtubule polymerization mitigates the fibrotic phenotype in fibrotic fibroblasts. These results reveal a potential link between PC length and fibroblast activation conserved across multiple fibrotic conditions. Our observations suggest that modulation of PC length might represent a novel therapeutic strategy for SSc and other treatment-resistant diseases associated with fibrosis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075072","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

MLL/WDR5 complex promotes recruitment of KIF2C to midbody to ensure MT depolymerization and furrow initiation during cytokinesis. MLL/WDR5复合体促进KIF2C向中间体募集，以确保细胞分裂过程中MT解聚和沟槽起始。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-17 DOI: 10.1242/jcs.263622

Avishek Kataria, Neeraja Hemalatha, Akash Chinchole, Shweta Tyagi

{"title":"MLL/WDR5 complex promotes recruitment of KIF2C to midbody to ensure MT depolymerization and furrow initiation during cytokinesis.","authors":"Avishek Kataria, Neeraja Hemalatha, Akash Chinchole, Shweta Tyagi","doi":"10.1242/jcs.263622","DOIUrl":"https://doi.org/10.1242/jcs.263622","url":null,"abstract":"Mixed-lineage leukemia (MLL) protein is a well-characterised epigenetic regulator whose non-canonical activities remain underappreciated. MLL has been shown to localize on the midbody and loss of this protein leads to binucleation. However, the critical role of the MLL complex in midbody formation remains underexplored. Here, we further characterize the localization of MLL and its associated protein WDR5 to the midbody. Loss of MLL/WDR5 results in defective midbody formation, which displays a wide midzone-like microtubule structure, along with chromosome bridges, resulting in binucleated cells. We show that MLL and WDR5 interact with kinesin 13 motor-KIF2C, and target it to the midbody. The depolymerase activity of KIF2C promotes correct localization of centralspindlin complex, compaction of midzone MTs, and finally, timely furrow initiation. Thus, we identify a previously unrecognized role for MLL and KIF2C in cytokinesis regulation. Together with earlier findings, this implicates them in the regulation of actin-microtubule cytoskeleton interface-pathways frequently altered in oncogenesis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075387","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

Lipid Nanoparticle-encapsulated Dnai1 mRNA rescues ciliary activity in primary ciliary dyskinesia mouse cell models. 脂质纳米颗粒包封Dnai1 mRNA可恢复原发性纤毛运动障碍小鼠细胞模型的纤毛活性。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-17 DOI: 10.1242/jcs.264068

Amanda J Smith, Patrick R Sears, Mirko Hennig, Rumpa B Bhattacharjee, Weining Yin, Hannah Golliher, Daniella Ishimaru, T Noelle Lombana, David J Lockhart, Brandon A Wustman, Lawrence E Ostrowski

{"title":"Lipid Nanoparticle-encapsulated Dnai1 mRNA rescues ciliary activity in primary ciliary dyskinesia mouse cell models.","authors":"Amanda J Smith, Patrick R Sears, Mirko Hennig, Rumpa B Bhattacharjee, Weining Yin, Hannah Golliher, Daniella Ishimaru, T Noelle Lombana, David J Lockhart, Brandon A Wustman, Lawrence E Ostrowski","doi":"10.1242/jcs.264068","DOIUrl":"https://doi.org/10.1242/jcs.264068","url":null,"abstract":"Primary ciliary dyskinesia (PCD) is a rare, genetically heterogenous disorder resulting from dysfunctional motile cilia that is characterized by chronic, progressive lung disease with currently no corrective therapies available. Here, we test the efficacy of selective organ targeting lipid nanoparticles (SORT-LNPs) that were optimized for potency and delivery to respiratory cells containing an mRNA coding for an axonemal protein to rescue ciliary activity in a murine culture model of PCD. Utilizing murine nasopharyngeal epithelial cell cultures (mNPEC) isolated from a conditional Dnai1 knockout mouse model of the known human PCD-associated gene DNAI1 homolog, we tested if SORT-LNPs containing an optimized Dnai1 mRNA could rescue ciliary activity. Treatment of differentiating and well-differentiated Dnai1 knockout mNPEC with SORT-LNP-Dnai1 mRNA led to a dose-dependent increase in levels of DNAI1 protein and incorporation into ciliary axonemes, resulting in rescued ciliary activity with normal ciliary beat frequency that persisted for over three weeks. These data support further clinical development of an mRNA-based therapeutic with LNP-mediated delivery as a treatment for PCD patients with disease-causing DNAI1 mutations.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080849","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

Prostaglandin E2 inhibits adipogenesis through the cilia-dependent activation of ROCK2. 前列腺素E2通过纤毛依赖性激活ROCK2抑制脂肪形成。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-16 DOI: 10.1242/jcs.264193

Mark D Lee, Keren I Hilgendorf

{"title":"Prostaglandin E2 inhibits adipogenesis through the cilia-dependent activation of ROCK2.","authors":"Mark D Lee, Keren I Hilgendorf","doi":"10.1242/jcs.264193","DOIUrl":"https://doi.org/10.1242/jcs.264193","url":null,"abstract":"Functional adipose tissue is essential for maintaining systemic metabolic homeostasis. Dysfunctional adipose tissue, characterized by increased fibrosis, hypoxia, and chronic inflammation, is often associated with obesity and promotes the onset of metabolic disease such as type 2 diabetes. During nutrient excess, adipose tissue function can be preserved by the generation of new adipocytes from adipocyte stem cells, illustrating the importance of identifying the physiological regulators of adipogenesis. Here, we discover a cilia-localized signaling pathway through which the pro-inflammatory lipid metabolite prostaglandin E2 (PGE2) suppresses adipogenesis. We demonstrate that PGE2 specifically signals through the E-type prostaglandin receptor 4 (EP4) localized to the primary cilium of adipocyte stem cells. Activation of ciliary EP4 initiates a cAMP-independent signaling cascade that activates the Rho-associated protein kinase 2 (ROCK2) resulting in the retention of actin stress fibers that prevent adipogenesis. These findings uncover a compartmentalized regulatory mechanism of adipogenesis by which primary cilia alter whole-cell physiology, cell fate, and ultimately adipose tissue expansion in response to an inflammatory hormone, offering insight into how chronic inflammation may contribute to adipose tissue dysfunction and metabolic disease progression.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069647","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

A conserved domain of Cfap298 governs left-right symmetry breaking in vertebrates. Cfap298的一个保守结构域控制着脊椎动物的左右对称性破缺。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-09-16 DOI: 10.1242/jcs.264129

Marvin Cortez, Cullen B Young, Katherine A Little, Daniel T Grimes, Danelle Devenport, Rebecca D Burdine

{"title":"A conserved domain of Cfap298 governs left-right symmetry breaking in vertebrates.","authors":"Marvin Cortez, Cullen B Young, Katherine A Little, Daniel T Grimes, Danelle Devenport, Rebecca D Burdine","doi":"10.1242/jcs.264129","DOIUrl":"10.1242/jcs.264129","url":null,"abstract":"Cfap298 is a highly conserved gene required for ciliary motility and dynein arm assembly, with known roles in Left-Right (LR) patterning in zebrafish and links to human ciliopathies. Here we describe a Cfap298 mutant allele, Cfap298ΔΔS, which selectively disrupts LR axis establishment in mice. Mutant embryos display organ laterality defects and abnormal Nodal, Pitx2, and Lefty1 expression, consistent with an early disruption in LR symmetry breaking. LR asymmetry is established by leftward fluid flow in the node, generated by planar-polarized cilia. Although cfap298 mutations are reported to affect planar polarity, we did not observe changes in cilia position, length, or CELSR1 localization within the node, suggesting that Cfap298ΔΔSfunctions at the level of cilia motility. Accordingly, cilia lining the trachea of Cfap298ΔΔS mutants fail to beat or beat incorrectly. Expression of the Cfap298ΔΔS variant in zebrafish partially rescues body curvature defects but fails to rescue LR defects of cfap298 (kurly) loss-of-function mutants. These results confirm a conserved role for Cfap298 in mammalian LR patterning and identify a novel region of CFAP298 with a conserved and essential role in cilia motility.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069594","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