Biomedical subjects

Jian Zhang

Publications and source records attributed to Jian Zhang.

16 recordsLinked to original sources

PubMed2026

Genetically Predicted Muscle Mass and Function in Relation to Deep Vein Thrombosis: A Two-step Mendelian Randomization Study Highlighting the Mediating Role of BMI.

BackgroundSarcopenia is observationally linked to venous thromboembolism, but the causal architecture and underlying biological pathways remain largely unclear. This study investigated the causal effects of sarcopenia-related traits on lower extremity deep vein thrombosis (DVT) and quantified potential mediating mechanisms.MethodsWe performed two-sample bidirectional Mendelian randomization (MR) and two-step mediation MR using large-scale GWAS data from UK Biobank, EMBL-EBI, and FinnGen. Exposures included appendicular lean mass (ALM), leg fat-free mass (LFM), hand grip strength, and walking pace. Eighteen candidate mediators were screened for indirect pathways.ResultsGenetically predicted higher ALM was significantly associated with increased DVT risk (FinnGen: OR = 1.288, 95% CI: 1.215-1.365, P < 0.001). Similar positive associations were observed for LFM (OR = 1.920-1.954, P < 0.001). By contrast, muscle functional traits - grip strength and walking pace - demonstrated no consistent causal effects. Reverse MR confirmed a unidirectional relationship. Body mass index (BMI) emerged as a pivotal mediator, accounting for 7.58% - 10.50% of the ALM-DVT effect and 52.74% - 62.73% of the LFM-DVT effect. Notably, the independent effect of ALM was largely attenuated after adjusting for metabolic confounders in multivariable MR.ConclusionGenetic predisposition to high muscle mass, rather than functional strength, increases DVT risk. This relationship appears to be significantly driven by metabolic adiposity, suggesting that the "muscle-vascular-coagulation" interaction is partly explained by body-size-related metabolic burden. Risk stratification should integrate muscle mass evaluation with comprehensive metabolic health assessments.

Humans↗

PubMed2026

Natural variation in SL6 determines fatty acid components and seed longevity in rice.

Seed longevity (SL) is vital for ensuring food security worldwide. However, the genetic basis of SL has been scarcely documented. Here, we report the cloning of a major SL locus, qSL6, encoding a fatty acyl-ACP thioesterase type B. SL6 is functionally conserved in regulating palmitic acid synthesis in seeds, conferring higher oxidation durability and SL in various species. Through the VP1-SL6 module, a seed desiccation-derived ABA signal is transmitted via VP1, which directly activates SL6 transcription to alter the fatty acid composition and elevate SL in seeds. The ancestral elite allele SL6HHZ harbors a virus-derived CT-rich motif cis-element in the 5'UTR, which serves as a universal, bidirectional mRNA stabilizer, contributing to the divergence between indica and japonica in terms of SL. Moreover, manipulating SL6 expression via marker-assisted selection or transgenic approaches notably improved SL in rice cultivars and F1 hybrids without affecting major agronomic traits. Our findings provided a promising genetic locus for improving SL in rice.

Oryza↗

PubMed2026

Loss of PBRM1 accelerates pancreatic cancer progression by inducing acquisition of mesenchymal phenotype and inflammatory cancer-associated fibroblasts reprogramming.

BACKGROUND: PBRM1 is an important subunit of the SWI/SNF complex, which broadly regulates gene transcription by chromatin remodeling. Genomic alterations of PBRM1 have been found in patients with pancreatic ductal adenocarcinoma (PDAC), but its molecular functions remain unclear. METHODS: Clinical relevance of PBRM1 was analyzed by using human PDAC samples and public genomic datasets. Mice with concomitant pancreas-specific Pbrm1 deletion in Kras-driven genetic PDAC models were generated. Single-cell transcriptomics were performed to determine tumor phenotype and microenvironment reprogramming. RESULTS: Reduction of PBRM1 expression was observed in human PDAC tissues and correlated with poor prognosis and metastasis. Pbrm1 loss promoted ductal metaplasia and delayed epithelial recovery in mice with caerulein-induced pancreatic injury. In PDAC model with either mutant Kras alone or in combination with Trp53 mutation, lack of Pbrm1 markedly accelerated tumor development and progression. Bulk transcriptomics and scRNA-seq identified reprogramming of both tumor compartment with mesenchymal phenotype acquisition and stroma compartment with inflammatory cancer-associated fibroblasts (iCAFs) transformation. Mechanistically, Pbrm1 deletion induced Zeb1 upregulation through epigenetic chromatin remodeling, thereby enhancing epithelial-mesenchymal and basal-like subtype transition. CONCLUSIONS: These findings indicated a tumor-suppressing role of PBRM1 in PDAC. PBRM1-deficient PDAC constitutes a specific subgroup of patients with aggressive phenotype and prognostic significance.

Animals↗

PubMed2026

Adjuvant apatinib therapy following concurrent chemoradiotherapy in patients with high-risk nasopharyngeal carcinoma: A multicenter, prospective phase 2 study.

PURPOSE: To assess the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with apatinib in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: This multicenter, prospective, phase II study enrolled patients with newly histologically confirmed LA-NPC, who were randomly assigned to receive CCRT followed by adjuvant apatinib (investigational arm) or CCRT alone (control arm). The investigational arm received 250 mg/day of oral apatinib administered every 28 days for up to six cycles after CCRT. The primary endpoint was 3-year progression-free survival (PFS) and secondary endpoints of overall survival (OS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) of 3-year, and safety. RESULTS: From July 2018 to September 2020, 44 and 44 patients were randomized into the CCRT-alone and CCRT and apatinib groups, respectively. The median follow-up duration 56 (range: 40.0-58.6) months. The survival outcomes were the 3-year PFS, OS, and DMFS rates in the adjuvant apatinib following CCRT group were significantly higher than those observed in the CCRT-alone group((PFS, 78.6%vs. 54.5%, p = 0.027; OS, 88.1% vs. 75.0%, p = 0.029; DMFS, 85.4%vs. 59.1%, p = 0.009). The 3-year LRFS was similar between the groups. The grade 3-4 treatment-related adverse events(TRAEs) were higher in the former group than in the latter. The most common grade 3-4 non-hematology-related adverse events were hypertension (14.3%), hand-foot syndrome (9.5%), increased transaminase levels (7.1%), and headache (7.1%). CONCLUSION: Apatinib significantly improved the treatment effects of CCRT for high-risk LA-NPC patients. Therefore, CCRT and adjuvant apatinib may represent a promising option for this patient population.

Adjuvant therapy↗

PubMed2026

Bibliometric analysis of retinoblastoma research over the past decade.

BACKGROUND: Retinoblastoma (RB), the most prevalent primary intraocular malignancy in children, has emerged as a model disease for exploring the molecular underpinnings of pediatric cancer. Over the past decade, research in this field has accelerated, propelled by advances in genomics, diagnostic imaging, targeted therapies, and global scientific collaboration. METHODS: This study systematically retrieved RB-related publications from 2015 to 2024 using the Web of Science Core Collection. A total of 4990 articles were included. CiteSpace and VOSviewer were employed to perform bibliometric and visual analyses across multiple dimensions, including countries, institutions, authors, journals, and thematic evolution. RESULTS: The United States and China were identified as the leading contributors, jointly accounting for over 40.55% of all publications. US-based journals led in both publication volume and citation impact, underscoring their global influence. Cluster analysis revealed 4 major research domains: clinical diagnosis, treatment, and prognosis; molecular mechanisms and signaling pathways; gene and protein function studies; and research methodologies and experimental models. CONCLUSION: RB research is transitioning into an era of precision oncology, characterized by molecular subtyping, novel therapeutic targets, and individualized treatment approaches. While diagnostic and therapeutic outcomes have markedly improved in high-income countries, significant disparities persist in low- and middle-income regions due to limited access to early detection and comprehensive care. Future priorities should include the refinement of preclinical models, investigation of drug resistance mechanisms, and promotion of international collaboration to standardize diagnostic and therapeutic strategies. These efforts are critical to improving global outcomes for children with RB.

Retinoblastoma↗

PubMed2026

Unraveling critical role of photosynthetic bacteria in sustaining aquatic microbial community stability and function through large-scale genomic data analyses.

The application of photosynthetic bacteria (PB) in water remediation has demonstrated exceptional advantages in terms of high efficiency and low-carbon benefits. However, the limited understanding of PB across natural aquatic environments has constrained the rational development of this strategy. Here, we analyzed 3198 genomic sequencing samples from seven types of natural aquatic ecosystems to investigate the distribution and functions of 42 PB genera commonly used in water remediation. The results showed that the average abundance of the targeted PB reached 9.83 %, with the highest value of 14.93 % observed in River, while Lake harbored the greatest PB genus diversity. PB genera exhibited high sensitivity to salinity, with Rhodoferax dominating freshwater habitats, whereas Rhodovulum was predominant in marine environments. Notably, co-occurrence network analysis revealed that PB were closely associated with microbial community stability and optimized interspecific interactions. Aquatic microbial communities with high PB abundance were characterized by efficient division-of-labor modules, accompanied by enhanced PB-associated functional potential for carbon fixation, denitrification, and sulfur oxidation. In summary, this study systematically elucidates the regional biogeographical patterns and ecological roles of PB in natural aquatic environments, providing a comprehensive scientific basis and theoretical guidance for the development and practical application of PB-based water remediation technologies.

Bacteria↗

PubMed2026

Allelic variation in UVR8 modulates thermotolerance-yield tradeoffs in plants.

Industrial activities have driven stratospheric ozone depletion, increasing surface UV-B radiation while exacerbating global warming. These changes limit crop productivity, alter species distributions, and disrupt plant metabolic processes, but the mechanisms linking energy signaling to heat-stress responses remain unclear. Here, we identify the photoreceptor UV RESISTANCE LOCUS 8b (OsUVR8b) as a substrate of SNF1-related protein kinase 1 (SnRK1) in rice and reveal a natural variation at its SnRK1-mediated phosphorylation site (Ser177) that is correlated with adaptation to tropical climates. The thermotolerant OsUVR8bAla177 accessions show geographic enrichment in low-latitude regions with elevated temperatures. Functional validation through prime editing demonstrated that a Ser177-to-Ala177 substitution enhances heat tolerance, whereas the reverse edit compromises it. Mechanistically, OsUVR8bSer177 exhibits reduced stability and an impaired capacity for scavenging reactive oxygen species under heat stress. The regulatory function of the OsUVR8b Ser177 phosphorylation site, a molecular switch that governs UVR8 stability and thermotolerance, can be functionally re-established across rice, Arabidopsis, tobacco, and soybean, indicating its preservation during domestication. Notably, OsUVR8bSer177 maintains higher fertility and yield under non-stress conditions, indicating a tradeoff between heat adaptation and productivity. Our findings thus establish this switch as a key regulator of the yield-resilience balance and a promising target for breeding of climate-resilient crops.

Thermotolerance↗

PubMed2026

Repeated low-level red-light therapy for improving asthenopic symptoms and accommodation in presbyopia.

BACKGROUND: To assess the short-term effectiveness of repeated low-level red light (RLRL) therapy in relieving asthenopia and enhancing accommodation in presbyopia. METHODS: This randomized, parallel-group, double-masked clinical trial enrolled adults with presbyopia and self-reported asthenopia. Participants were allocated using computer-generated randomization and randomly assigned at a 1:1 ratio to RLRL or sham groups. Blinding included participants, examiners, assessors, and statisticians. The primary outcome was the change from baseline in the Computer Vision Syndrome Questionnaire (CVS-Q) score at day 31. Secondary outcomes were the change in accommodative amplitude (AA), Near Activity Visual Questionnaire (NAVQ) score, habitual near visual acuity, near-addition power, accommodative facility, positive and negative relative accommodation, binocular cross-cylinder response, and accommodative convergence-to-accommodation ratio. Continuous outcomes were analyzed using linear mixed-effects models. RESULTS: Sixty-four of 66 randomized participants (aged 41-62 years) completed the 1-month trial. At day 31, RLRL showed greater improvement than sham in CVS-Q score (adjusted mean difference, -1.75 points; 95% CI, -3.10 to -0.39), binocular AA (1.09 D; 95% CI, 0.37 to 1.82), and NAVQ score (-8.07 points; 95% CI, -14.17 to -1.97). The effect on AA was most pronounced in a subgroup of eyes with baseline amplitude >2.0 D (adjusted mean difference 1.33 D; 95% CI 0.32-2.34). Other measures did not differ between groups at each visit. No treatment-related adverse events were reported. Adherence was similar between groups (mean compliance: 98.2% vs 97.5%). CONCLUSIONS: Short-term treatment with RLRL significantly reduced asthenopic symptoms and improved accommodative amplitude in individuals with presbyopia.Trial registration: NCT06745661 (registered December 8, 2024).

Humans↗

PubMed2026

Identification and analysis of HD-ZIP transcription factors that regulate salt gland development and salt tolerance in Limonium bicolor.

Soil salinity severely constrains agricultural production. Elucidating the salt-tolerance mechanisms of halophytes can provide innovative approaches for improving the salt tolerance of crop plants. In this study, we performed genome-wide identification and analysis of 36 LbHDZ genes encoding homeodomain-leucine zipper (HD-ZIP) transcription factors in Limonium bicolor, a typical recretohalophyte that excretes excess salt ions through specialized salt glands. Expression profiling across different stages of salt gland development, as well as in various tissues under salt stress, indicated that multiple LbHDZ genes are involved in regulating salt gland development and salt tolerance. Among these genes, LbHDZ14 (a member of the HD-ZIP II subfamily) exhibited sustained high expression during the critical period of salt gland formation, while its transcript levels were significantly downregulated in leaves and roots under salt stress. Subsequent experiments demonstrated that LbHDZ14 is localized in the nucleus and negatively regulates salt gland density and salt tolerance by directly binding to the promoter of LbGDSL, a positive regulator of salt gland development. In conclusion, this study reveals the expression patterns of LbHDZ genes in L. bicolor, characterizes the functional mechanism of LbHDZ14, further elucidates the regulatory network underlying salt gland development, and provides candidate genes for enhancing crop salt tolerance.

Plumbaginaceae↗

PubMed2025

C6ORF120 regulates hepatic lipid metabolism through PPAR signaling pathway in metabolic dysfunction-associated steatotic liver disease.

Background Emerging evidence indicates that C6ORF120 is highly expressed in the liver and may modulate immune responses in various hepatic disorders. However, its role in hepatic lipid metabolism and metabolic dysfunction-associated steatotic liver disease (MASLD) is unexplored. This study aimed to elucidate the effects and potential mechanisms of C6ORF120 on hepatic lipogenesis. Methods C6ORF120 expression in MASLD was assessed using patient serum and the Gene Expression Omnibus (GEO) database. A high-fat diet-induced MASLD model was established in C6orf120-KO rats. Fatty acid-induced lipid accumulation models were generated in primary hepatocytes, HepG2 and Huh7 cells. These models were employed to investigate the effects of C6ORF120 on hepatic lipogenesis and MASLD progression. Results C6ORF120 expression was significantly upregulated in MASLD patients and obese rat models. Genetic deletion of C6ORF120 markedly alleviated high-fat diet-induced steatosis in the liver of rats. In vitro, C6orf120 gene deficiency attenuated lipid accumulation and suppressed key lipogenic genes (such as fatty acid synthase (Fasn), phospho-acetyl coenzyme carboxylase (p-ACC), sterol regulatory element binding protein-1c (Srebp1c)) in primary hepatocytes and HepG2 cells. Conversely, C6ORF120 overexpression increased lipid accumulation in HepG2 cells. RNA sequencing analysis showed that lipid metabolism pathway and peroxisome proliferators activated receptor (PPAR) signaling pathway were significantly altered in the liver of C6orf120-KO rats. We demonstrated that C6ORF120 may regulate lipid metabolism through the hepatic PPARα, which is involved in fatty acid production and lipid oxidation. Further, we found that serum C6ORF120 expression was correlated with clinical indicators in patients with MASLD. Conclusion This study preliminarily revealed a novel function for C6ORF120 in hepatic lipid metabolism via affecting the PPAR pathway. The result identifies C6ORF120 as a novel regulator of hepatic lipid metabolism through PPARα-dependent mechanisms, offering potential therapeutic targets for MASLD.

Lipid Metabolism↗

PubMed2025

The modern expansion of Dscam1 isoform diversity in Drosophila is linked to fitness and immunity.

Drosophila melanogaster Down Syndrome cell adhesion molecule 1 (Dscam1) gene encodes 38,016 diverse cell surface receptor proteins via alternative splicing, which have both nervous and immune functions. However, it remains elusive why organisms have evolved such an astonishing diversity of isoforms. Here, we show that fitness and immunity properties have driven the modern evolution of Dscam1 isoform diversity. We assess multiple aspects of fly fitness in deletion mutants harboring exon 4, 6, or 9 clusters, respectively, reducing ectodomain isoform diversity stepwise from 18,612 to 396. All fitness-related traits generally improved as the potential number of isoforms increased; however, the magnitude of the changes varied remarkably in a variable cluster-specific manner. Correlation analysis revealed that fitness-related traits were much more sensitive to reductions in Dscam1 diversity compared to canonical neuronal self/non-self discrimination. We conclude that the role of Dscam1 isoforms in canonical neuronal self-avoidance and self/non-self discrimination is mediated by a small fraction of all isoforms (<1/10), whereas a separate role essential for other developmental contexts and resistances, likely in fitness and immunity, requires almost full isoform diversity. Thus, fitness and immunity properties, rather than canonical neuronal functions, are the dominant drivers during the modern diversification of the Dscam1 isoform. Our findings suggest that Dscam1 diversity is closely linked to adaptation and species diversification in arthropods.

Animals↗

PubMed2025

Systematically investigating and identifying bacteriocins in the human gut microbiome.

Human gut microbiota produces unmodified bacteriocins, natural antimicrobial peptides that protect against pathogens and regulate host physiology. However, current bioinformatic tools limit the comprehensive investigation of bacteriocins' biosynthesis, obstructing research into their biological functions. Here, we introduce IIBacFinder, a superior analysis pipeline for identifying unmodified class II bacteriocins. Through large-scale bioinformatic analysis and experimental validation, we demonstrate their widespread distribution across the bacterial kingdom, with most being habitat specific. Analyzing over 280,000 bacterial genomes, we reveal the diverse potential of human gut bacteria to produce these bacteriocins. Guided by meta-omics analysis, we synthesized 26 hypothetical bacteriocins from gut commensal species, with 16 showing antibacterial activities. Further ex vivo tests show minimal impact of narrow-spectrum bacteriocins on human fecal microbiota. Our study highlights the huge biosynthetic potential of unmodified bacteriocins in the human gut, paving the way for understanding their biological functions and health implications.

Humans↗

PubMed2025

Integrative Genomic, Transcriptomic and Epigenomic Analysis Reveals cis-regulatory Contributions to High-altitude Adaptation in Tibetan Pigs.

The Qinghai-Tibet Plateau, characterized by its extreme environmental conditions, presents significant challenges to life, making it an ideal region for studying adaptation and evolution. Tibetan pigs, known for their high genetic diversity and exceptional adaptability to high altitudes, serve as excellent models for investigating high-altitude adaptation. While previous studies have extensively identified genetic determinants associated with high-altitude adaptation, the molecular mechanisms, particularly cis-regulatory patterns, remain poorly understood. Here, we conducted a selective sweep analysis using 484 genomes from Chinese and Western pig breeds across various altitudes, revealing 38.56 Mb of genomic regions under selection in Tibetan pigs. Enrichment analysis identified the lung as the primary functional tissue involved in high-altitude adaptation, supported by tissue-specific transcriptional and regulatory patterns observed between Tibetan and Meishan pigs (low altitude). By integrating genomic, RNA-seq, ATAC-seq, and H3K27ac HiChIP data, we constructed comprehensive enhancer-promoter regulatory maps of candidate genes and pinpointed promising genetic determinants associated with high-altitude adaptation, including SNPs in EPAS1, KLF13, SPRED1, and CFD. These loci were predicted to influence chromatin accessibility and the interactions of regulatory elements, with altered binding strength of relevant transcription factors. Further in vitro experiments confirmed that these loci function as allele-specific enhancers, modulating the expression of target genes. Our findings elucidate the regulatory basis of high-altitude adaptation in Tibetan pigs and provide valuable insights for exploring hypoxia-related diseases in livestock and humans.

Animals↗

PubMed2025

HnRNPR promotes non-small cell lung cancer progression by protecting XB130 mRNA from XRN1- and DIS3L2-mediated degradation.

The adaptor protein XB130 is critically implicated in tumorigenesis. However, the mechanisms regulating its expression in tumors are not well understood. Our previous studies have identified hnRNPR as a potential binding protein of XB130 3'UTR in non-small cell lung cancer (NSCLC). This study aimed to clarify hnRNPR's role in NSCLC progression and its specific mechanisms regulating XB130 expression. The expression of hnRNPR in NSCLC and normal tissues was assessed using NSCLC tissue microarray and the TCGA database. Subsequently, in vitro and in vivo experiments were conducted to investigate the impact of hnRNPR on NSCLC cell proliferation and epithelial-mesenchymal transition (EMT) by modulating XB130 expression. The underlying molecular mechanisms of hnRNPR regulating XB130 expression were explored utilizing a range of molecular biology techniques including Western blotting, Real-time quantitative PCR, Immunohistochemistry, Dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation. We identified the overexpression of hnRNPR in NSCLC, with heightened hnRNPR levels significantly associated with poor prognosis in patients with lung adenocarcinoma. Functionally, hnRNPR overexpression promoted NSCLC cell proliferation and EMT and activated the Akt signaling pathway. Mechanistically, hnRNPR protected XB130 mRNA from XRN1- and DIS3L2-mediated degradation by binding to specific regions within XB130 3'UTR, consequently elevating XB130 expression. Lastly, XB130 overexpression counteracted the effects of hnRNPR silencing on NSCLC cells. Overall, our study unveils the potential of targeting the hnRNPR/XB130 axis as a promising therapeutic strategy for NSCLC.

Humans↗

PubMed2025

Insights into dill (Anethum graveolens) flavor formation via integrative analysis of chromosomal-scale genome, metabolome and transcriptome.

INTRODUCTION: Dill (Anethum graveolens) is a significant medicinal herb belonging to the Apiaceae family. Owing to its high levels of volatile organic compounds (VOCs), dill is commonly utilized for essential oil extraction and medicine purpose. However, the biosynthesis of the crucial VOC in dill remains obscure. OBJECTIVES: Identify the key VOCs related to the flavor formation in dill and dissect the regulatory mechanism of their synthesis. METHODS: The dill chromosomal-level genome was constructed by PacBio HiFi, Hi-C, and BGISEQ second generation sequencing and assembly. The VOCs in dill leaves were identified through GC-MS. The potential mechanism involved in regulating the VOC accumulation in dill flavor formation was analyzed by multi-omics analysis. RESULTS: A 1.17 Gb chromosome-scale genome of dill with a contig N50 of 10.78 Mb was constructed. A total of 46,538 genes were annotated across 11 assembled chromosomes. Comparative genomics analysis suggested that transposable element insertions, especially LTR-Gypsy, have contributed to the evolution and expansion of the dill genome. The flavor formation of dill was mainly attributed to terpenoids, especially α-phellandrene, β-ocimene, and o-cymene. The contribution of expansion and replication of terpenoid synthesis pathway genes, especially terpene synthase (TPS), to the abundant terpenoid production of dill was identified. Differential gene expression patterns observed at various developmental stages and tissues provided key candidate genes for the regulation of terpenoid synthesis, as well as transcription factors. The different accumulation of esters and aromatics also affected the flavor formation of dill. The key genes implicated in the synthesis of anethole, namely AIS and AMT were further identified. CONCLUSION: This study constructed the chromosome level genome and identified the main VOCs and related key genes in flavor formation of dill, shedding lights on our understanding of terpenoid biosynthesis but also offered guidance for future genetic research on molecular breeding in Anethum graveolens.

Transcriptome↗

PubMed2023

A systematic CRISPR screen reveals redundant and specific roles for Dscam1 isoform diversity in neuronal wiring.

Drosophila melanogaster Down syndrome cell adhesion molecule 1 (Dscam1) encodes 19,008 diverse ectodomain isoforms via the alternative splicing of exon 4, 6, and 9 clusters. However, whether individual isoforms or exon clusters have specific significance is unclear. Here, using phenotype-diversity correlation analysis, we reveal the redundant and specific roles of Dscam1 diversity in neuronal wiring. A series of deletion mutations were performed from the endogenous locus harboring exon 4, 6, or 9 clusters, reducing to 396 to 18,612 potential ectodomain isoforms. Of the 3 types of neurons assessed, dendrite self/non-self discrimination required a minimum number of isoforms (approximately 2,000), independent of exon clusters or isoforms. In contrast, normal axon patterning in the mushroom body and mechanosensory neurons requires many more isoforms that tend to associate with specific exon clusters or isoforms. We conclude that the role of the Dscam1 diversity in dendrite self/non-self discrimination is nonspecifically mediated by its isoform diversity. In contrast, a separate role requires variable domain- or isoform-related functions and is essential for other neurodevelopmental contexts, such as axonal growth and branching. Our findings shed new light on a general principle for the role of Dscam1 diversity in neuronal wiring.

Animals↗