BMC Biology最新文献

{"title":"Hypoxia and Foxn1 alter the proteomic signature of dermal fibroblasts to redirect scarless wound healing to scar-forming skin wound healing in Foxn1−/− mice","authors":"Barbara Gawronska-Kozak, Sylwia Machcinska-Zielinska, Katarzyna Walendzik, Marta Kopcewicz, Mirva Pääkkönen, Joanna Wisniewska","doi":"10.1186/s12915-024-01990-2","DOIUrl":"https://doi.org/10.1186/s12915-024-01990-2","url":null,"abstract":"Foxn1−/− deficient mice are a rare model of regenerative skin wound healing among mammals. In wounded skin, the transcription factor Foxn1 interacting with hypoxia-regulated factors affects re-epithelialization, epithelial-mesenchymal transition (EMT) and dermal white adipose tissue (dWAT) reestablishment and is thus a factor regulating scar-forming/reparative healing. Here, we hypothesized that transcriptional crosstalk between Foxn1 and Hif-1α controls the switch from scarless (regenerative) to scar-present (reparative) skin wound healing. To verify this hypothesis, we examined (i) the effect of hypoxia/normoxia and Foxn1 signalling on the proteomic signature of Foxn1−/− (regenerative) dermal fibroblasts (DFs) and then (ii) explored the effect of Hif-1α or Foxn1/Hif-1α introduced by a lentiviral (LV) delivery vector to injured skin of regenerative Foxn1−/− mice with particular attention to the remodelling phase of healing. We showed that hypoxic conditions and Foxn1 stimulation modified the proteome of Foxn1−/− DFs. Hypoxic conditions upregulated DF protein profiles, particularly those related to extracellular matrix (ECM) composition: plasminogen activator inhibitor-1 (Pai-1), Sdc4, Plod2, Plod1, Lox, Loxl2, Itga2, Vldlr, Ftl1, Vegfa, Hmox1, Fth1, and F3. We found that Pai-1 was stimulated by hypoxic conditions in regenerative Foxn1−/− DFs but was released by DFs to the culture media exclusively upon hypoxia and Foxn1 stimulation. We also found higher levels of Pai-1 protein in DFs isolated from Foxn1+/+ mice (reparative/scar-forming) than in DFs isolated from Foxn1−/− (regenerative/scarless) mice and triggered by injury increase in Foxn1 and Pai-1 protein in the skin of mice with active Foxn1 (Foxn1+/+ mice). Then, we demonstrated that the introduction of Foxn1 and Hif-1α via lentiviral injection into the wounded skin of regenerative Foxn1−/− mice activates reparative/scar-forming healing by increasing the wounded skin area and decreasing hyaluronic acid deposition and the collagen type III to I ratio. We also identified a stimulatory effect of LV-Foxn1 + LV-Hif-1α injection in the wounded skin of Foxn1−/− mice on Pai-1 protein levels. The present data highlight the effect of hypoxia and Foxn1 on the protein profile and functionality of regenerative Foxn1−/− DFs and demonstrate that the introduction of Foxn1 and Hif-1α into the wounded skin of regenerative Foxn1−/− mice activates reparative/scar-forming healing.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mrp-3 gene is involved in haem efflux and detoxification in a blood-feeding nematode","authors":"Danni Tong, Fei Wu, Xueqiu Chen, Zhendong Du, Jingru Zhou, Jingju Zhang, Yi Yang, Aifang Du, Guangxu Ma","doi":"10.1186/s12915-024-02001-0","DOIUrl":"https://doi.org/10.1186/s12915-024-02001-0","url":null,"abstract":"Haem is essential but toxic for metazoan organisms. Auxotrophic nematodes can acquire sufficient haem from the environment or their hosts in the meanwhile eliminate or detoxify excessive haem through tightly controlled machinery. In previous work, we reported a role of the unique transporter protein HRG-1 in the haem acquisition and homeostasis of parasitic nematodes. However, little is known about the haem efflux and detoxification via ABC transporters, particularly the multiple drug resistance proteins (MRPs). Here, we further elucidate that a member of the mrp family (mrp-3) is involved in haem efflux and detoxification in a blood-feeding model gastrointestinal parasite, Haemonchus contortus. This gene is haem-responsive and dominantly expressed in the intestine and inner membrane of the hypodermis of this parasite. RNA interference of mrp-3 resulted in a disturbance of genes (e.g. hrg-1, hrg-2 and gst-1) that are known to be involved in haem homeostasis and an increased formation of haemozoin in the treated larvae and lethality in vitro, particularly when exposed to exogenous haem. Notably, the nuclear hormone receptor NHR-14 appears to be associated the regulation of mrp-3 expression for haem homeostasis and detoxification. Gene knockdown of nhr-14 and/or mrp-3 increases the sensitivity of treated larvae to exogenous haem and consequently a high death rate (> 80%). These findings demonstrate that MRP-3 and the associated molecules are essential for haematophagous nematodes, suggesting novel intervention targets for these pathogens in humans and animals.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogeny and evolution of hemipteran insects based on expanded genomic and transcriptomic data.","authors":"Nan Song, Miao-Miao Wang, Wei-Chao Huang, Zhi-Yi Wu, Renfu Shao, Xin-Ming Yin","doi":"10.1186/s12915-024-01991-1","DOIUrl":"10.1186/s12915-024-01991-1","url":null,"abstract":"<p><strong>Background: </strong>Hemiptera is the fifth species-rich order of insects and the most species-rich order of hemimetabolous insects, including numerous insect species that are of agricultural or medical significance. Despite much effort and recent advance in inferring the Hemiptera phylogeny, some high-level relationships among superfamilies remain controversial.</p><p><strong>Results: </strong>We sequenced the genomes of 64 hemipteran species from 15 superfamilies and the transcriptomes of two additional scale insect species, integrating them with existing genomic and transcriptomic data to conduct a comprehensive phylogenetic analysis of Hemiptera. Our datasets comprise an average of 1625 nuclear loci of 315 species across 27 superfamilies of Hemiptera. Our analyses supported Cicadoidea and Cercopoidea as sister groups, with Membracoidea typically positioned as the sister to Cicadoidea + Cercopoidea. In most analyses, Aleyrodoidea was recovered as the sister group of all other Sternorrhyncha. A sister-group relationship was supported between Coccoidea and Aphidoidea + Phylloxeroidea. These relationships were further supported by four-cluster likelihood mapping analyses across diverse datasets. Our ancestral state reconstruction indicates phytophagy as the primary feeding strategy for Hemiptera as a whole. However, predation likely represents an ancestral state for Heteroptera, with several phytophagous lineages having evolved from predatory ancestors. Certain lineages, like Lygaeoidea, have undergone a reversal transition from phytophagy to predation. Our divergence time estimation placed the diversification of hemipterans to be between 60 and 150 million years ago.</p><p><strong>Conclusions: </strong>By expanding phylogenomic taxon sampling, we clarified the superfamily relationships within the infraorder Cicadomorpha. Our phylogenetic analyses supported the sister-group relationship between the superfamilies Cicadoidea and Cercopoidea, and the superfamily Membracoidea as the sister to Cicadoidea + Cercopoidea. Our divergence time estimation supported the close association of hemipteran diversification with the evolutionary success and adaptive radiation of angiosperms during the Cretaceous period.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104624","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}

{"title":"Introgression drives adaptation to the plateau environment in a subterranean rodent.","authors":"Yukun Kang, Zhicheng Wang, Kang An, Qiqi Hou, Zhiming Zhang, Junhu Su","doi":"10.1186/s12915-024-01986-y","DOIUrl":"10.1186/s12915-024-01986-y","url":null,"abstract":"<p><strong>Background: </strong>Introgression has repeatedly been shown to play an important role in the adaptation of species to extreme environments, yet how introgression enables rodents with specialized subterranean lifestyle to acclimatize to high altitudes is still unclear. Myospalacinae is a group of subterranean rodents, among which the high-altitude plateau zokors (Eospalax baileyi) and the low-altitude Gansu zokors (E. cansus) are sympatrically distributed in the grassland ecosystems of the Qinghai-Tibet Plateau (QTP). Together, they provide a model for the study of the role of introgression in the adaptation of low-altitude subterranean rodents to high altitudes.</p><p><strong>Results: </strong>Applying low-coverage whole-genome resequencing and population genetics analyses, we identified evidence of adaptive introgression from plateau zokors into Gansu zokors, which likely facilitated the adaptation of the latter to the high-altitude environment of the QTP. We identified positively selected genes with functions related to energy metabolism, cardiovascular system development, calcium ion transport, and response to hypoxia which likely made critical contributions to adaptation to the plateau environment in both plateau zokors and high-altitude populations of Gansu zokors.</p><p><strong>Conclusions: </strong>Introgression of genes associated with hypoxia adaptation from plateau zokors may have played a role in the adaptation of Gansu zokors to the plateau environment. Our study provides new insights into the understanding of adaptive evolution of species on the QTP and the importance of introgression in the adaptation of species to high-altitude environments.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104622","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}

{"title":"Identification of a novel DNA oxidative damage repair pathway, requiring the ubiquitination of the histone variant macroH2A1.1.","authors":"Khalid Ouararhni, Flore Mietton, Jamal S M Sabir, Abdulkhaleg Ibrahim, Annie Molla, Raed S Albheyri, Ali T Zari, Ahmed Bahieldin, Hervé Menoni, Christian Bronner, Stefan Dimitrov, Ali Hamiche","doi":"10.1186/s12915-024-01987-x","DOIUrl":"10.1186/s12915-024-01987-x","url":null,"abstract":"<p><strong>Background: </strong>The histone variant macroH2A (mH2A), the most deviant variant, is about threefold larger than the conventional histone H2A and consists of a histone H2A-like domain fused to a large Non-Histone Region responsible for recruiting PARP-1 to chromatin. The available data suggest that the histone variant mH2A participates in the regulation of transcription, maintenance of heterochromatin, NAD⁺ metabolism, and double-strand DNA repair.</p><p><strong>Results: </strong>Here, we describe a novel function of mH2A, namely its implication in DNA oxidative damage repair through PARP-1. The depletion of mH2A affected both repair and cell survival after the induction of oxidative lesions in DNA. PARP-1 formed a specific complex with mH2A nucleosomes in vivo. The mH2A nucleosome-associated PARP-1 is inactive. Upon oxidative damage, mH2A is ubiquitinated, PARP-1 is released from the mH2A nucleosomal complex, and is activated. The in vivo-induced ubiquitination of mH2A, in the absence of any oxidative damage, was sufficient for the release of PARP-1. However, no release of PARP-1 was observed upon treatment of the cells with either the DNA alkylating agent MMS or doxorubicin.</p><p><strong>Conclusions: </strong>Our data identify a novel pathway for the repair of DNA oxidative lesions, requiring the ubiquitination of mH2A for the release of PARP-1 from chromatin and its activation.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104621","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}

{"title":"Phylogenomics analysis of Scutellaria (Lamiaceae) of the world.","authors":"Yinghui Wang, Chao Xu, Xing Guo, Yan Wang, Yanyi Chen, Jie Shen, Chunnian He, Yan Yu, Qiang Wang","doi":"10.1186/s12915-024-01982-2","DOIUrl":"10.1186/s12915-024-01982-2","url":null,"abstract":"<p><strong>Background: </strong>Scutellaria, a sub-cosmopolitan genus, stands as one of the Lamiaceae family's largest genera, encompassing approximately 500 species found in both temperate and tropical montane regions. Recognized for its significant medicinal properties, this genus has garnered attention as a research focus, showcasing anti-cancer, anti-inflammatory, antioxidant, and hepatoprotective qualities. Additionally, it finds application in agriculture and horticulture. Comprehending Scutellaria's taxonomy is pivotal for its effective utilization and conservation. However, the current taxonomic frameworks, primarily based on morphological characteristics, are inadequate. Despite several phylogenetic studies, the species relationships and delimitations remain ambiguous, leaving the genus without a stable and reliable classification system.</p><p><strong>Results: </strong>This study analyzed 234 complete chloroplast genomes, comprising 220 new and 14 previously published sequences across 206 species, subspecies, and varieties worldwide. Phylogenetic analysis was conducted using six data matrices through Maximum Likelihood and Bayesian Inference, resulting in a robustly supported phylogenetic framework for Scutellaria. We propose three subgenera, recommending the elevation of Section Anaspis to subgeneric rank and the merging of Sections Lupulinaria and Apeltanthus. The circumscription of Subgenus Apeltanthus and Section Perilomia needs to be reconsidered. Comparative analysis of chloroplast genomes highlighted the IR/SC boundary feature as a significant taxonomic indicator. We identified a total of 758 SSRs, 558 longer repetitive sequences, and ten highly variable regions, including trnK-rps16, trnC-petN, petN-psbM, accD-psaI, petA-psbJ, rpl32-trnL, ccsA-ndhD, rps15-ycf1, ndhF, and ycf1. These findings serve as valuable references for future research on species identification, phylogeny, and population genetics.</p><p><strong>Conclusions: </strong>The phylogeny of Scutellaria, based on the most comprehensive sample collection to date and complete chloroplast genome analysis, has significantly enhanced our understanding of its infrageneric relationships. The extensive examination of chloroplast genome characteristics establishes a solid foundation for the future development and utilization of Scutellaria, an important medicinal plant globally.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104623","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}

{"title":"Alterations of pleiotropic neuropeptide-receptor gene couples in Cetacea.","authors":"Raul Valente, Miguel Cordeiro, Bernardo Pinto, André Machado, Filipe Alves, Isabel Sousa-Pinto, Raquel Ruivo, L Filipe C Castro","doi":"10.1186/s12915-024-01984-0","DOIUrl":"10.1186/s12915-024-01984-0","url":null,"abstract":"<p><strong>Background: </strong>Habitat transitions have considerable consequences in organism homeostasis, as they require the adjustment of several concurrent physiological compartments to maintain stability and adapt to a changing environment. Within the range of molecules with a crucial role in the regulation of different physiological processes, neuropeptides are key agents. Here, we examined the coding status of several neuropeptides and their receptors with pleiotropic activity in Cetacea.</p><p><strong>Results: </strong>Analysis of 202 mammalian genomes, including 41 species of Cetacea, exposed an intricate mutational landscape compatible with gene sequence modification and loss. Specifically for Cetacea, in the 12 genes analysed we have determined patterns of loss ranging from species-specific disruptive mutations (e.g. neuropeptide FF-amide peptide precursor; NPFF) to complete erosion of the gene across the cetacean stem lineage (e.g. somatostatin receptor 4; SSTR4).</p><p><strong>Conclusions: </strong>Impairment of some of these neuromodulators may have contributed to the unique energetic metabolism, circadian rhythmicity and diving response displayed by this group of iconic mammals.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104619","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}

{"title":"Genome binding properties of Zic transcription factors underlie their changing functions during neuronal maturation.","authors":"Melyssa S Minto, Jesús Emiliano Sotelo-Fonseca, Vijyendra Ramesh, Anne E West","doi":"10.1186/s12915-024-01989-9","DOIUrl":"10.1186/s12915-024-01989-9","url":null,"abstract":"<p><strong>Background: </strong>The Zic family of transcription factors (TFs) promote both proliferation and maturation of cerebellar granule neurons (CGNs), raising the question of how a single, constitutively expressed TF family can support distinct developmental processes. Here we use an integrative experimental and bioinformatic approach to discover the regulatory relationship between Zic TF binding and changing programs of gene transcription during postnatal CGN differentiation.</p><p><strong>Results: </strong>We first established a bioinformatic pipeline to integrate Zic ChIP-seq data from the developing mouse cerebellum with other genomic datasets from the same tissue. In newborn CGNs, Zic TF binding predominates at active enhancers that are co-bound by developmentally regulated TFs including Atoh1, whereas in mature CGNs, Zic TF binding consolidates toward promoters where it co-localizes with activity-regulated TFs. We then performed CUT&RUN-seq in differentiating CGNs to define both the time course of developmental shifts in Zic TF binding and their relationship to gene expression. Mapping Zic TF binding sites to genes using chromatin looping, we identified the set of Zic target genes that have altered expression in RNA-seq from Zic1 or Zic2 knockdown CGNs.</p><p><strong>Conclusions: </strong>Our data show that Zic TFs are required for both induction and repression of distinct, developmentally regulated target genes through a mechanism that is largely independent of changes in Zic TF binding. We suggest that the differential collaboration of Zic TFs with other TF families underlies the shift in their biological functions across CGN development.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104620","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}

{"title":"The roles of cell wall polysaccharides in response to waterlogging stress in Brassica napus L. root.","authors":"Jijun Li, Yuting Zhang, Yahui Chen, Yijing Wang, Zhihua Zhou, Jinxing Tu, Liang Guo, Xuan Yao","doi":"10.1186/s12915-024-01972-4","DOIUrl":"10.1186/s12915-024-01972-4","url":null,"abstract":"<p><strong>Background: </strong>Brassica napus L. (B. napus) is susceptible to waterlogging stress during different cultivation periods. Therefore, it is crucial to enhance the resistance to waterlogging stress to achieve a high and stable yield of B. napus.</p><p><strong>Results: </strong>Here we observed significant differences in the responses of two B. napus varieties in root under waterlogging stress. The sensitive variety (23651) exhibited a more pronounced and rapid reduction in cell wall thickness and root integrity compared with the tolerant variety (Santana) under waterlogging stress. By module clustering analysis based on transcriptome data, we identified that cell wall polysaccharide metabolism responded to waterlogging stress in root. It was found that pectin content was significantly reduced in the sensitive variety compared with the tolerant variety. Furthermore, transcriptome analysis revealed that the expression of two homologous genes encoding polygalacturonase-inhibiting protein 2 (PGIP2), involved in polysaccharide metabolic pathways, was highly upregulated in root of the tolerant variety under waterlogging stress. BnaPGIP2s probably confer waterlogging resistance by inhibiting the activity of polygalacturonases (PGs), which in turn reduces the degradation of the pectin backbone polygalacturonic acid.</p><p><strong>Conclusions: </strong>Our findings demonstrate that cell wall polysaccharides in root plays a vital role in response to the waterlogging stress and provide a theoretical foundation for breeding waterlogging resistance in B. napus varieties.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104625","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}

{"title":"Foxg1 regulates translation of neocortical neuronal genes, including the main NMDA receptor subunit gene, Grin1.","authors":"Osvaldo Artimagnella, Elena Sabina Maftei, Mauro Esposito, Remo Sanges, Antonello Mallamaci","doi":"10.1186/s12915-024-01979-x","DOIUrl":"10.1186/s12915-024-01979-x","url":null,"abstract":"<p><strong>Background: </strong>Mainly known as a transcription factor patterning the rostral brain and governing its histogenesis, FOXG1 has been also detected outside the nucleus; however, biological meaning of that has been only partially clarified.</p><p><strong>Results: </strong>Prompted by FOXG1 expression in cytoplasm of pallial neurons, we investigated its implication in translational control. We documented the impact of FOXG1 on ribosomal recruitment of Grin1-mRNA, encoding for the main subunit of NMDA receptor. Next, we showed that FOXG1 increases GRIN1 protein level by enhancing the translation of its mRNA, while not increasing its stability. Molecular mechanisms underlying this activity included FOXG1 interaction with EIF4E and, possibly, Grin1-mRNA. Besides, we found that, within murine neocortical cultures, de novo synthesis of GRIN1 undergoes a prominent and reversible, homeostatic regulation and FOXG1 is instrumental to that. Finally, by integrated analysis of multiple omic data, we inferred that FOXG1 is implicated in translational control of hundreds of neuronal genes, modulating ribosome engagement and progression. In a few selected cases, we experimentally verified such inference.</p><p><strong>Conclusions: </strong>These findings point to FOXG1 as a key effector, potentially crucial to multi-scale temporal tuning of neocortical pyramid activity, an issue with profound physiological and neuropathological implications.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055025","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}