IF 6.4 1区生物学

eLife Pub Date : 2024-12-24 DOI: 10.7554/eLife.93646

David Oestreicher, Shashank Chepurwar, Kathrin Kusch, Vladan Rankovic, Sangyong Jung, Nicola Strenzke, Tina Pangrsic

{"title":"CaBP1 and 2 enable sustained CaV1.3 calcium currents and synaptic transmission in inner hair cells.","authors":"David Oestreicher, Shashank Chepurwar, Kathrin Kusch, Vladan Rankovic, Sangyong Jung, Nicola Strenzke, Tina Pangrsic","doi":"10.7554/eLife.93646","DOIUrl":"10.7554/eLife.93646","url":null,"abstract":"To encode continuous sound stimuli, the inner hair cell (IHC) ribbon synapses utilize calcium-binding proteins (CaBPs), which reduce the inactivation of their CaV1.3 calcium channels. Mutations in the CABP2 gene underlie non-syndromic autosomal recessive hearing loss DFNB93. Besides CaBP2, the structurally related CaBP1 is highly abundant in the IHCs. Here, we investigated how the two CaBPs cooperatively regulate IHC synaptic function. In Cabp1/2 double-knockout mice, we find strongly enhanced CaV1.3 inactivation, slowed recovery from inactivation and impaired sustained exocytosis. Already mild IHC activation further reduces the availability of channels to trigger synaptic transmission and may effectively silence synapses. Spontaneous and sound-evoked responses of spiral ganglion neurons in vivo are strikingly reduced and strongly depend on stimulation rates. Transgenic expression of CaBP2 leads to substantial recovery of IHC synaptic function and hearing sensitivity. We conclude that CaBP1 and 2 act together to suppress voltage- and calcium-dependent inactivation of IHC CaV1.3 channels in order to support sufficient rate of exocytosis and enable fast, temporally precise and indefatigable sound encoding.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The satiety hormone cholecystokinin gates reproduction in fish by controlling gonadotropin secretion. 饱腹激素胆囊收缩素通过控制促性腺激素的分泌来抑制鱼类的繁殖。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-24 DOI: 10.7554/eLife.96344

Lian Hollander-Cohen, Omer Cohen, Miriam Shulman, Tomer Aiznkot, Pierre Fontanaud, Omer Revah, Patrice Mollard, Matan Golan, Berta Levavi-Sivan

{"title":"The satiety hormone cholecystokinin gates reproduction in fish by controlling gonadotropin secretion.","authors":"Lian Hollander-Cohen, Omer Cohen, Miriam Shulman, Tomer Aiznkot, Pierre Fontanaud, Omer Revah, Patrice Mollard, Matan Golan, Berta Levavi-Sivan","doi":"10.7554/eLife.96344","DOIUrl":"10.7554/eLife.96344","url":null,"abstract":"Life histories of oviparous species dictate high metabolic investment in the process of gonadal development leading to ovulation. In vertebrates, these two distinct processes are controlled by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively. While it was suggested that a common secretagogue, gonadotropin-releasing hormone (GnRH), oversees both functions, the generation of loss-of-function fish challenged this view. Here, we reveal that the satiety hormone cholecystokinin (CCK) is the primary regulator of this axis in zebrafish. We found that FSH cells express a CCK receptor, and our findings demonstrate that mutating this receptor results in a severe hindrance to ovarian development. Additionally, it causes a complete shutdown of both gonadotropins secretion. Using in-vivo and ex-vivo calcium imaging of gonadotrophs, we show that GnRH predominantly activates LH cells, whereas FSH cells respond to CCK stimulation, designating CCK as the bona fide FSH secretagogue. These findings indicate that the control of gametogenesis in fish was placed under different neural circuits, that are gated by CCK.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bridging the gap between presynaptic hair cell function and neural sound encoding. 弥合突触前毛细胞功能和神经声音编码之间的差距。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-24 DOI: 10.7554/eLife.93749

Lina María Jaime Tobón, Tobias Moser

{"title":"Bridging the gap between presynaptic hair cell function and neural sound encoding.","authors":"Lina María Jaime Tobón, Tobias Moser","doi":"10.7554/eLife.93749","DOIUrl":"10.7554/eLife.93749","url":null,"abstract":"Neural diversity can expand the encoding capacity of a circuitry. A striking example of diverse structure and function is presented by the afferent synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea. Presynaptic active zones at the pillar IHC side activate at lower IHC potentials than those of the modiolar side that have more presynaptic Ca2+ channels. The postsynaptic SGNs differ in their spontaneous firing rates, sound thresholds, and operating ranges. While a causal relationship between synaptic heterogeneity and neural response diversity seems likely, experimental evidence linking synaptic and SGN physiology has remained difficult to obtain. Here, we aimed at bridging this gap by ex vivo paired recordings of murine IHCs and postsynaptic SGN boutons with stimuli and conditions aimed to mimic those of in vivo SGN characterization. Synapses with high spontaneous rate of release (SR) were found predominantly on the pillar side of the IHC. These high SR synapses had larger and more temporally compact spontaneous EPSCs, lower voltage thresholds, tighter coupling of Ca2+ channels and vesicular release sites, shorter response latencies, and higher initial release rates. This study indicates that synaptic heterogeneity in IHCs directly contributes to the diversity of spontaneous and sound-evoked firing of SGNs.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long non-coding RNA Malat1 fine-tunes bone homeostasis and repair by orchestrating cellular crosstalk and β-catenin-OPG/Jagged1 pathway. 长链非编码RNA Malat1通过协调细胞串扰和β-catenin-OPG/Jagged1通路微调骨稳态和修复。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-23 DOI: 10.7554/eLife.98900

Yongli Qin, Jumpei Shirakawa, Cheng Xu, Ruge Chen, Xu Yang, Courtney Ng, Shinichi Nakano, Mahmoud Elguindy, Zhonghao Deng, Kannanganattu V Prasanth, Moritz F Eissmann, Shinichi Nakagawa, William M Ricci, Baohong Zhao

{"title":"Long non-coding RNA Malat1 fine-tunes bone homeostasis and repair by orchestrating cellular crosstalk and β-catenin-OPG/Jagged1 pathway.","authors":"Yongli Qin, Jumpei Shirakawa, Cheng Xu, Ruge Chen, Xu Yang, Courtney Ng, Shinichi Nakano, Mahmoud Elguindy, Zhonghao Deng, Kannanganattu V Prasanth, Moritz F Eissmann, Shinichi Nakagawa, William M Ricci, Baohong Zhao","doi":"10.7554/eLife.98900","DOIUrl":"10.7554/eLife.98900","url":null,"abstract":"The IncRNA Malat1 was initially believed to be dispensable for physiology due to the lack of observable phenotypes in Malat1 knockout (KO) mice. However, our study challenges this conclusion. We found that both Malat1 KO and conditional KO mice in the osteoblast lineage exhibit significant osteoporosis. Mechanistically, Malat1 acts as an intrinsic regulator in osteoblasts to promote osteogenesis. Interestingly, Malat1 does not directly affect osteoclastogenesis but inhibits osteoclastogenesis in a non-autonomous manner in vivo via integrating crosstalk between multiple cell types, including osteoblasts, osteoclasts, and chondrocytes. Our findings substantiate the existence of a novel remodeling network in which Malat1 serves as a central regulator by binding to β-catenin and functioning through the β-catenin-OPG/Jagged1 pathway in osteoblasts and chondrocytes. In pathological conditions, Malat1 significantly promotes bone regeneration in fracture healing. Bone homeostasis and regeneration are crucial to well-being. Our discoveries establish a previous unrecognized paradigm model of Malat1 function in the skeletal system, providing novel mechanistic insights into how a lncRNA integrates cellular crosstalk and molecular networks to fine tune tissue homeostasis, remodeling and repair.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Virus adaptation to heparan sulfate comes with capsid stability tradeoff. 病毒对硫酸肝素的适应伴随着衣壳稳定性的权衡。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-23 DOI: 10.7554/eLife.98441

Han Kang Tee, Simon Crouzet, Arunima Muliyil, Gregory Mathez, Valeria Cagno, Matteo Dal Peraro, Aleksandar Antanasijevic, Sophie Clément, Caroline Tapparel

{"title":"Virus adaptation to heparan sulfate comes with capsid stability tradeoff.","authors":"Han Kang Tee, Simon Crouzet, Arunima Muliyil, Gregory Mathez, Valeria Cagno, Matteo Dal Peraro, Aleksandar Antanasijevic, Sophie Clément, Caroline Tapparel","doi":"10.7554/eLife.98441","DOIUrl":"10.7554/eLife.98441","url":null,"abstract":"Because of high mutation rates, viruses constantly adapt to new environments. When propagated in cell lines, certain viruses acquire positively charged amino acids on their surface proteins, enabling them to utilize negatively charged heparan sulfate (HS) as an attachment receptor. In this study, we used enterovirus A71 (EV-A71) as the model and demonstrated that, unlike the parental MP4 variant, the cell-adapted strong HS-binder MP4-97R/167 G does not require acidification for uncoating and releases its genome in the neutral or weakly acidic environment of early endosomes. We experimentally confirmed that this pH-independent entry is not associated with the use of HS as an attachment receptor but rather with compromised capsid stability. We then extended these findings to another HS-dependent strain. In summary, our data indicate that the acquisition of capsid mutations conferring affinity for HS comes together with decreased capsid stability and allows EV-A71 to enter the cell via a pH-independent pathway. This pH-independent entry mechanism boosts viral replication in cell lines but may prove deleterious in vivo, especially for enteric viruses crossing the acidic gastric environment before reaching their primary replication site, the intestine. Our study thus provides new insight into the mechanisms underlying the in vivo attenuation of HS-binding EV-A71 strains. Not only are these viruses hindered in tissues rich in HS due to viral trapping, as generally accepted, but our research reveals that their diminished capsid stability further contributes to attenuation in vivo. This underscores the complex relationship between HS-binding, capsid stability, and viral fitness, where increased replication in cell lines coincides with attenuation in harsh in vivo environments like the gastrointestinal tract.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Frequency-specific cortico-subcortical interaction in continuous speaking and listening. 持续说与听中特定频率的皮质-皮质下相互作用。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-23 DOI: 10.7554/eLife.97083

Omid Abbasi, Nadine Steingräber, Nikos Chalas, Daniel S Kluger, Joachim Gross

引用次数: 0

The emergence of visual category representations in infants' brains. 婴儿大脑中视觉类别表征的出现。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-23 DOI: 10.7554/eLife.100260

Xiaoqian Yan, Sarah Shi Tung, Bella Fascendini, Yulan Diana Chen, Anthony M Norcia, Kalanit Grill-Spector

{"title":"The emergence of visual category representations in infants' brains.","authors":"Xiaoqian Yan, Sarah Shi Tung, Bella Fascendini, Yulan Diana Chen, Anthony M Norcia, Kalanit Grill-Spector","doi":"10.7554/eLife.100260","DOIUrl":"10.7554/eLife.100260","url":null,"abstract":"Organizing the continuous stream of visual input into categories like places or faces is important for everyday function and social interactions. However, it is unknown when neural representations of these and other visual categories emerge. Here, we used steady-state evoked potential electroencephalography to measure cortical responses in infants at 3-4 months, 4-6 months, 6-8 months, and 12-15 months, when they viewed controlled, gray-level images of faces, limbs, corridors, characters, and cars. We found that distinct responses to these categories emerge at different ages. Reliable brain responses to faces emerge first, at 4-6 months, followed by limbs and places around 6-8 months. Between 6 and 15 months response patterns become more distinct, such that a classifier can decode what an infant is looking at from their brain responses. These findings have important implications for assessing typical and atypical cortical development as they not only suggest that category representations are learned, but also that representations of categories that may have innate substrates emerge at different times during infancy.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single cells tell it all. 单细胞说明了一切。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-23 DOI: 10.7554/eLife.105042

Margaret Hines, Elias Oxman, Pooja Chauhan, Irene Zohn

引用次数: 0

A novel human pluripotent stem cell gene activation system identifies IGFBP2 as a mediator in the production of haematopoietic progenitors in vitro. 一种新的人类多能干细胞基因激活系统鉴定出IGFBP2是体外造血祖细胞产生的中介。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-23 DOI: 10.7554/eLife.94884

Paolo Petazzi, Telma Ventura, Francesca Paola Luongo, Heather McClafferty, Alisha May, Helen Alice Taylor, Michael J Shipston, Nicola Romanò, Lesley M Forrester, Pablo Menendez, Antonella Fidanza

{"title":"A novel human pluripotent stem cell gene activation system identifies IGFBP2 as a mediator in the production of haematopoietic progenitors in vitro.","authors":"Paolo Petazzi, Telma Ventura, Francesca Paola Luongo, Heather McClafferty, Alisha May, Helen Alice Taylor, Michael J Shipston, Nicola Romanò, Lesley M Forrester, Pablo Menendez, Antonella Fidanza","doi":"10.7554/eLife.94884","DOIUrl":"10.7554/eLife.94884","url":null,"abstract":"A major challenge in the stem cell biology field is the ability to produce fully functional cells from induced pluripotent stem cells (iPSCs) that are a valuable resource for cell therapy, drug screening, and disease modelling. Here, we developed a novel inducible CRISPR-mediated activation strategy (iCRISPRa) to drive the expression of multiple endogenous transcription factors (TFs) important for in vitro cell fate and differentiation of iPSCs to haematopoietic progenitor cells. This work has identified a key role for IGFBP2 in developing haematopoietic progenitors. We first identified nine candidate TFs that we predicted to be involved in blood cell emergence during development, then generated tagged gRNAs directed to the transcriptional start site of these TFs that could also be detected during single-cell RNA sequencing (scRNAseq). iCRISPRa activation of these endogenous TFs resulted in a significant expansion of arterial-fated endothelial cells expressing high levels of IGFBP2, and our analysis indicated that IGFBP2 is involved in the remodelling of metabolic activity during in vitro endothelial to haematopoietic transition. As well as providing fundamental new insights into the mechanisms of haematopoietic differentiation, the broader applicability of iCRISPRa provides a valuable tool for studying dynamic processes in development and for recapitulating abnormal phenotypes characterised by ectopic activation of specific endogenous gene expression in a wide range of systems.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Base editing of Ptbp1 in neurons alleviates symptoms in a mouse model of Parkinson's disease. 神经元中Ptbp1的碱基编辑减轻了帕金森病小鼠模型的症状。

IF 6.4 1区生物学

eLife Pub Date : 2024-12-23 DOI: 10.7554/eLife.97180

Desiree Böck, Maria Wilhelm, Jonas Mumenthaler, Daniel Fabio Carpanese, Peter I Kulcsár, Simon d'Aquin, Alessio Cremonesi, Anahita Rassi, Johannes Häberle, Tommaso Patriarchi, Gerald Schwank

{"title":"Base editing of Ptbp1 in neurons alleviates symptoms in a mouse model of Parkinson's disease.","authors":"Desiree Böck, Maria Wilhelm, Jonas Mumenthaler, Daniel Fabio Carpanese, Peter I Kulcsár, Simon d'Aquin, Alessio Cremonesi, Anahita Rassi, Johannes Häberle, Tommaso Patriarchi, Gerald Schwank","doi":"10.7554/eLife.97180","DOIUrl":"10.7554/eLife.97180","url":null,"abstract":"Parkinson's disease (PD) is a multifactorial disease caused by irreversible progressive loss of dopaminergic neurons (DANs). Recent studies have reported the successful conversion of astrocytes into DANs by repressing polypyrimidine tract binding protein 1 (PTBP1), which led to the rescue of motor symptoms in a chemically-induced mouse model of PD. However, follow-up studies have questioned the validity of this astrocyte-to-DAN conversion model. Here, we devised an adenine base editing strategy to downregulate PTBP1 in astrocytes and neurons in a chemically-induced PD mouse model. While PTBP1 downregulation in astrocytes had no effect, PTBP1 downregulation in neurons of the striatum resulted in the expression of the DAN marker tyrosine hydroxylase (TH) in non-dividing neurons, which was associated with an increase in striatal dopamine concentrations and a rescue of forelimb akinesia and spontaneous rotations. Phenotypic analysis using multiplexed iterative immunofluorescence imaging further revealed that most of these TH-positive cells co-expressed the dopaminergic marker DAT and the pan-neuronal marker NEUN, with the majority of these triple-positive cells being classified as mature GABAergic neurons. Additional research is needed to fully elucidate the molecular mechanisms underlying the expression of the observed markers and understand how the formation of these cells contributes to the rescue of spontaneous motor behaviors. Nevertheless, our findings support a model where downregulation of neuronal, but not astrocytic, PTBP1 can mitigate symptoms in PD mice.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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