Search Results (4,631)

Tooth development or odontogenesis is a complex morphogenetic process that requires tightly regulated interactions between the oral epithelium and mesenchyme of neural crest origin. In this narrative review, we compile existing knowledge regarding gene regulatory networks and epigenetic factors throughout tooth development from initiation to eruption. Signaling between the epithelium and mesenchyme is mediated by four conserved pathways—Wnt/β-catenin, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Sonic hedgehog (Shh)—which operate iteratively and interact through extensive crosstalk at each developmental stage. Transcription factors, such as PAX9, MSX1, PITX2, and LEF1, interpret these signals to control cell fate decisions and differentiation. Epigenetic modifications, including DNA methylation, histone modifications, and microRNA-mediated regulation, provide additional layers of control that fine-tune gene expression programs. Unlike existing reviews that address these regulatory mechanisms separately, here we integrate signaling pathways, transcription factor networks, epigenetic regulation, human genetic disorders, dental stem cell biology, and recent single-cell transcriptomic insights into a unified framework. We discuss opportunities to apply developmental biology knowledge towards regenerative dentistry goals, including iPSC-derived dental models and spatially resolved multi-omics approaches, while acknowledging the considerable gap between preclinical findings and clinical applications. Full article

Background/Objectives: Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a triplet repeat expansion in the Fmr1 gene leading to the loss of Fragile X Messenger Ribonucleoprotein (Fmr1 protein). The loss of Fmr1 protein modulates many cell biological processes and leads to the emergence of intellectual disability and autism. FXS is modeled in Fmr1-KO mice that display features consistent with human FXS, including hypersensitivity, cognitive and learning deficits, hyperactivity and audiogenic seizures. Here, we investigated the effect of auditory stimulation during a range of developmental stages on recognition memory and sociability deficits in Fmr1-KO mice. Methods: Fmr1-KO mice were subjected to auditory stimulation for 2 min three times a day at one-hour intervals for 5 days at the nursing, juvenile and adult stages. The animals were tested for social interaction and novel object recognition at 2 to 3 months old. Results: During auditory stimulation, the wild running phenotype was observed in the Fmr1-KO juvenile animals and two animals at the nursing stage experienced status epilepticus and died. Fmr1-KO animals showed social deficits compared to both the control and animals exposed to auditory stimulation at the juvenile stage. In the novel object recognition task, auditory stimulation was more effective at the nursing and juvenile stages. Conclusions: These data show that auditory stimulation may be an effective way to restore cognitive and social deficits in FXS. Full article

As sessile organisms, plants must continuously perceive and integrate external environmental cues with internal developmental signals to optimize growth, reproduction, and survival. Central to this adaptive capacity is the ubiquitin-proteasome system (UPS), the primary pathway for selective protein degradation in eukaryotes. Within the UPS, BTB (Broad-Complex, Tramtrack, and Bric-à-brac) proteins serve as critical substrate adaptors for the Cullin3 (CUL3)-based E3 ubiquitin ligase complex. These proteins play indispensable roles in plant growth, development, hormone signaling, and responses to abiotic stresses. Recent advances have revealed the remarkable functional versatility of BTB proteins, implicating them in the regulation of photomorphogenesis, root architecture, flowering time, stress resilience, and yield-related traits. With 80 BTB-encoding genes in Arabidopsis thaliana and key orthologs identified in major crops—including of rice (Oryza sativa), soybean (Glycine max), and maize (Zea mays)—BTB proteins act as molecular “bridges” that integrate developmental programs with environmental stress signals. This review summarizes the structural features, classification, and multifaceted functions of plant BTB proteins, with an emphasis on their roles in growth regulation, abiotic stress tolerance, light signaling, and agricultural productivity. We further discuss their mechanisms in ubiquitin-dependent proteolysis, transcriptional regulation, and signal integration, offering insights into their potential as targets for engineering climate-resilient crops and advancing sustainable agriculture. Full article

Background/Objectives: The coordination of flowering and dormancy represents a fundamental adaptive strategy for perennial plant survival. Recent studies have demonstrated that AIL1 homologs act as integrators of short-day signals, playing pivotal roles in seasonal growth cessation and dormancy regulation in poplar. Despite these advances, whether AIL1-mediated regulatory mechanisms are conserved in Platanus acerifolia, a species with distinct phylogenetic and ecological characteristics, remains an open question. Methods: In this study, two AIL1 homologs, PaAIL1a and PaAIL1b, were isolated from P. acerifolia. Their biological functions were systematically investigated through sequence analysis, spatiotemporal expression profiling, environmental stress treatments, yeast one-hybrid assays, and luciferase (LUC) transient expression assays. Results: PaAIL1s (PaAIL1a and PaAIL1b) exhibited ubiquitous expression across diverse tissues and organs, functioning as mediators of photoperiod and temperature signaling to orchestrate bud dormancy regulation. Interaction and activation assays placed these factors downstream of PaFUL proteins. While displaying functional redundancy in dormancy induction and floral development, the paralogs underwent distinct subfunctionalization: PaAIL1a specifically regulated flowering initiation and dormancy release, whereas PaAIL1b acted predominantly during the ecodormancy phase. Conclusions: These results establish PaAIL1 genes as critical integrators of environmental signals and developmental programs, governing seasonal growth dynamics in this species. Full article

Mitogen-activated protein kinase kinase kinases (MAPKKKs) play important roles in plant responses to abiotic stresses; however, the function of SiMAPKKK17 in mediating drought tolerance in foxtail millet remains unclear. In this study, the expression pattern, subcellular localization, and biological function of SiMAPKKK17 were investigated to clarify its role in the drought stress response. Tissue expression analysis showed that SiMAPKKK17 was expressed across developmental stages and in multiple organs, with the highest transcript level observed at the booting stage and comparatively higher expression in vegetative tissues, including roots, stems, and leaves. Subcellular localization analysis demonstrated that SiMAPKKK17 was localized to both the plasma membrane and the nucleus, suggesting potential involvement in membrane-associated signal transduction and nuclear regulatory processes. To evaluate its function, foxtail millet lines overexpressing SiMAPKKK17 were generated and subjected to drought stress. Compared with wild-type plants, the overexpression lines exhibited enhanced drought tolerance, as indicated by greener and more upright upper leaves, higher aboveground fresh weight, greater plant height, and larger leaf area under drought conditions. Transcriptome analysis of OE4 and WT plants under drought stress identified 3919 upregulated genes and 2965 downregulated genes in OE4 compared with WT. These differentially expressed genes were mainly enriched in chloroplast-related cellular components, as well as biological processes and metabolic pathways related to cellular amide metabolism, ion transport, carbon metabolism, photosynthesis, carbon fixation, purine metabolism, and amino acid biosynthesis. Taken together, these results indicate that SiMAPKKK17 acts as a positive regulator of drought tolerance in foxtail millet, potentially through modulation of photosynthesis- and metabolism-related pathways. This study provides evidence for the molecular mechanisms underlying drought tolerance in foxtail millet and identifies SiMAPKKK17 as a promising candidate gene for the development of drought-resistant cultivars. Full article

Transcriptome atlases can be used to examine the spatiotemporal dynamics of gene expression, thereby enabling the generation of genome-wide resources for understanding complex biological processes. In the silkworm Bombyx mori, transcriptomes serve as crucial datasets for elucidating the mechanisms underlying economically important traits. In this study, we integrated 832 transcriptome datasets across all developmental stages and tissues and performed whole-genome-scale transcriptome sequencing (RNAseq) on five critical tissues from silkworm strains Xian8 and 9211. We identified 5773 and 3323 housekeeping genes expressed across all developmental stages and tissues, respectively, and these genes were primarily enriched in cellular signaling, transport, structural organization, DNA repair, and RNA processing pathways. We also identified 27 stage-specific genes and 58 tissue-specific genes, providing candidate markers for future single-cell and spatial transcriptomics. A large number of alternative splicing events were detected from 832 NGS samples, indicating the critical roles of alternative splicing in silkworm development. Interestingly, only 10 long-read full-length transcriptome samples from Xian8 and 9211 yielded results comparable to the NGS in terms of novel genes and alternative splicing events, and these multi-tissue comparative analyses also revealed significant differences in alternative splicing patterns, underlining the necessity of long-read sequencing for such research. These datasets not only advance functional genomics research in Lepidoptera but also provide molecular signatures for silkworm strain-specific comparisons and association analyses with differential phenotypes. Silkworm pan-transcriptomics, by analyzing multidimensional transcriptional regulatory networks and gene-expression dynamics, can facilitate multidisciplinary integration and accelerate the breeding of high-yield and high-quality silkworm varieties. Full article

Soil salinity remains a major constraint to rice productivity, particularly during early developmental stages when plants are highly sensitive to osmotic and ionic stress. In this study, we evaluated 201 genetically diverse rice genotypes from the 3K Rice Diversity Panel to investigate stage-specific mechanisms of salinity tolerance and develop machine learning-based predictive models for rapid phenotypic screening. Morphological and physiological traits were measured under control and saline conditions at germination and early seedling stages to derive Stress Tolerance Indices (STIs). The average membership function value (AMFV), calculated from multi-trait STI profiles, effectively captured variation in salinity responses and enabled classification of genotypes into five tolerance categories. Genome-wide association analysis using high-density SNP markers identified 36 significant marker–trait associations, including potentially novel SNPs on chromosomes 1 and 12. Several loci co-localized with candidate genes (LTR1, LGF1, OsCPS4, OsNCX7, and OsNHX4), while functional SNPs within genes (OsDRP2C, RLCK168, and OsMed37_2) and non-synonymous variants (qSVII11.1 and qSNaK3.1) further supported their candidacy in salinity tolerance. Mining favourable SNPs of causal genes identified superior multilocus combinations consistent with STI-based phenotypic patterns, with genotype 91-382 emerging as the strongest performer, exhibiting enhanced Na⁺ exclusion, K⁺ retention, and biomass resilience across developmental stages. To address multicollinearity among STI traits, we applied cross-validated LASSO (germination) and Elastic Net (early seedling) models, achieving high predictive accuracy and revealing a developmental shift from biomass-driven tolerance at germination to ion-regulatory processes at the seedling stage. Independent validation showed strong agreement between predicted and observed AMFVs. By integrating physiological indices, GWAS-derived SNP signals, and regularized machine learning approaches, this study provides a robust framework for identifying elite donors and accelerating breeding for salt-tolerant rice. Full article

Diapause hormone (DH) is an important endocrine substance capable of influencing diapause in Lepidoptera moths that is encoded by the neuropeptide hormone DH-PBAN gene. Imidazole derivative KK-42 is a synthetic insect growth regulator that can affect diapause in Lepidoptera moths, and appears to have an opposite physiological function to DH. To test the hypothesis that KK-42 may be operating through DH to affect diapause, here, we used two Lepidoptera species Bombyx mori L. and Antheraea pernyi that enter egg and pupal diapause, respectively, through examining whether KK-42 can influence DH-PBAN and some associated mRNA expression. We found that the protein sequences of DH-PBAN in insects were highly variable, although the PRXamide C-terminus was conserved. We also found that KK-42 induced significant up-regulation and prolonged expression duration of DH-PBAN in both A. pernyi and B. mori pupae, as well as in trimolter larvae of B. mori that were induced by the application of KK-42 from the normal tetramolter larvae. In addition, KK-42 can significantly upregulate glutamic acid decarboxylase (GAD) expression in B. mori in transcriptome data. Our findings suggested that KK-42 influences diapause by upregulating GAD expression, promoting DH accumulation to prolong the secretion time of DH-PBAN. Full article

Ethnopharmacological relevance. Withania somnifera (L.) Dunal, widely used in traditional medical systems such as Ayurveda, Unani, and Middle Eastern folk medicine, is valued for its adaptogenic, anti-inflammatory, neuroprotective, antimicrobial, and anticancer properties. These activities are primarily attributed to withanolides, with Withaferin A recognized as one of the most bioactive constituents. Although traditional preparations often rely on the root, leaf use provides a more sustainable alternative and may yield significant quantities of active metabolites. Identifying efficient, modern extraction technologies that can enhance the recovery of bioactive compounds from leaves is essential for developing effective, standardized ethnopharmacological formulations. Materials and methods. Plants of W. somnifera grown from seeds were subjected to different environmental conditions (control, drought, cold, yeast extract treatment). Leaves were extracted using Pressurized Cyclic Solid–Liquid Extraction (PCSLE) with hydroalcoholic solvents and compared with conventional infusion of dried leaves. Extracts were fractionated with solvents of varying polarity and analyzed by TLC, HPLC, and NMR for quantification of Withaferin A. Expression levels of key withanolide-biosynthetic genes (CAS, SMT1, DWARF1, CYP71, CYP76) were assessed using qRT-PCR. Antimicrobial activity of pure Withaferin A, aqueous extract, and hydroalcoholic PCSLE extract was evaluated through MIC and MBC assays against Gram-positive and Gram-negative strains. Cytotoxic activity was measured via MTT assays in six human cancer cell lines after 3, 6, and 24 h of treatment. Results. PCSLE yielded substantially higher levels of Withaferin A than traditional infusion, especially in medium-polarity fractions (chloroform and ethyl acetate), with concentrations reaching 0.70% in fresh leaf mass (4.8% dry weight), compared to 0.11% obtained by infusion. Gene expression analysis revealed that 24-week-old plants exhibited the highest transcription of withanolide-biosynthetic genes, and drought stress significantly upregulated CAS, SMT1, DWARF1, CYP71, and CYP716, indicating enhanced metabolic flux toward withanolide production. Hydroalcoholic PCSLE extracts showed broad-spectrum antimicrobial activity, with MIC and MBC values comparable to pure Withaferin A and demonstrating bactericidal effects against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. The aqueous extract showed activity only against Gram-positive strains. Cytotoxicity assays demonstrated an optimistic, dose-dependent reduction in cell viability across all tumour cell lines treated with the hydroalcoholic PCSLE extract, closely mirroring the activity of pure Withaferin A and consistently exceeding the effect of the aqueous extract. IC50 values confirmed the high bioactive content of PCSLE extracts and suggested mechanisms like those known for Withaferin A. Conclusions. PCSLE proved to be a highly efficient extraction technology for obtaining leaf extracts rich in Withaferin A, outperforming conventional extraction methods while exploiting sustainable plant tissue. Developmental stage and drought stress significantly modulated the expression of genes involved in withanolide biosynthesis, highlighting agronomic strategies capable of enhancing metabolite production. Hydroalcoholic PCSLE extracts exhibited antimicrobial and cytotoxic activities comparable to pure Withaferin A, supporting their relevance as promising therapeutic candidates. These findings advocate for the use of W. somnifera leaves as a sustainable source of bioactive compounds and demonstrate that advanced extraction technologies can contribute to the development of innovative ethnopharmacological preparations for antimicrobial and anticancer applications. Full article

Background/Objectives: This article is a narrative review that examines the development of attachment from intrauterine life to the first thousand days of a child’s life, integrating psychoanalytic, neuroscientific, genetic, and cross-cultural perspectives. Biological, relational, neurological, and cultural factors interact and shape individual differences in socio-emotional functioning. This paper aims to propose a reinterpretation of early attachment, describing it as both a clinical and relational phenomenon and an adaptive process inscribed in human evolutionary history, according to the Four-Domain Integrative Framework described herein. Methods: The review examined three main areas of evidence: early attachment characteristics, cross-cultural caregiving variations, and genetic and epigenetic mechanisms underlying environmental sensitivity. Results: The review first identified seven characteristics of early attachment (proximity seeking, emotional attunement, intrauterine experiences, maternal holding, security patterns, brain plasticity, and maternal stress) which represent developmental mechanisms that generate individual differences in trust, self-regulation, resilience, and psychopathological vulnerability. Second, cross-cultural variations in six distinct caregiving contexts were examined, demonstrating that secure attachment emerges through culturally specific pathways, differentially influencing motor development, sleep patterns, hypothalamic–pituitary–adrenal axis maturation, and social skills. Finally, the differential susceptibility model was provided through the analysis of five genetic and epigenetic systems (oxytocin receptor gene, serotonin transporter gene, dopamine receptor gene, glucocorticoid receptor methylation, and fetal programming) that modulate environmental sensitivity. Conclusions: Biological, relational, neurological, and cultural factors interact and shape individual differences in socio-emotional functioning. Full article

The reciprocal relationship between genes and nutrients, known as nutrigenetics and nutrigenomics, has been established in many studies. However, current investigations of maternal and neonatal nutrition using a precision nutrition approach focused on genomics are limited, especially in the Middle East and North Africa (MENA) region. This review aims to summarize the impacts of the dietary micronutrients, folic acid, thiamine, and cobalamin on optimal health outcomes during pregnancy, fetal development, lactation, and infant growth. In this review, the roles of folic acid, thiamine, and cobalamin are discussed in the context of various aspects of pregnancy, such as preconception, fetal development, and lactation, highlighting how genetic events occurring during developmental periods can have consequential impacts on health outcomes later in life. Deficiency rates and related health consequences as well as the prevalence of genetic mutations related to these nutrients of interest in the MENA region are also elaborated on. How to advance knowledge and applications of precision nutrition, how genes interact with the neurochemical changes during pregnancy, and how this interaction impacts maternal eating behaviors, and consequently fetal development and infant and child growth and health, should be further explored in future studies. This includes taking advantage of cutting-edge technologies and the role of artificial intelligence in this endeavor. Full article

The MADS-box transcription factor (TF) family constitutes a critical class of transcriptional regulators in plants, playing pivotal roles in diverse developmental processes. MIKC-type proteins represent Type II MADS-box TFs that widely function in regulating floral organ development and reproductive growth in plants. In this study, a total of 38 MIKC-type MADS TFs were identified from the sorghum genome, distributed across nine chromosomes. Based on sequence alignments and phylogenetic analysis, these 38 SbMIKC genes (SbMIKCs) were further classified into 10 distinct subfamilies. The expression profiling of these SbMIKCs across multiple tissues revealed five major patterns, among which SbMIKC17 exhibited relatively abundant transcript levels during grain development in sorghum. Further assays confirmed that the protein encoded by SbMIKC17 localizes to the nucleus without self-transactivation activity in yeast. Integrated results from DNA affinity purification sequencing (DAP-seq), dual-luciferase assays, and yeast one-hybrid experiments demonstrate that SbMIKC17 binds to the promoter of SbAGPS1 and activates its activity, as well as enhance the promoter activities of SbBt1, SbGBSSI, SbSSIIa, and SbISA1 simultaneously. Collectively, these findings suggest that the MIKC-type MADS member of SbMIKC17 serves as a potential transcriptional regulator in starch biosynthesis in sorghum. Full article

Severe southern soybean crinkle leaf disease (SSCLD) reduces soybean seed yield by approximately 40%. Identifying the genes that control SSCLD is crucial for breeding resistant varieties and elucidating the molecular mechanisms underlying SSCLD infection. In this study, recombinant inbred lines (RILs, n = 236) derived from a cross between Nannong1138-2 (NN1138-2) and Zhengxiaodou (ZXD) were used as experimental materials. A field trial employing a randomized block design was conducted in four environments across two locations, Nanning (2019–2021) and Du’an (2020) in Guangxi, to identify the disease severity grades of SSCLD in the field. QTLs controlling SSCLD were detected via a genetic map constructed using 3255 SLAF (specific locus amplified fragment) markers from the recombinant inbred lines. RT–qPCR was used to analyze candidate gene expression at major effect loci. The results revealed that eight SSCLD-associated QTLs were identified on chromosomes 3, 6, 12, and 17. Notably, the qw12-1 locus on chromosome 12 was detected across three developmental stages in three of the four environments, explaining 10.18–58.20% of the phenotypic variation. RT–qPCR analysis of 12 disease resistance-related genes within the qw12-1 interval revealed that GLYMA_12G233000 and GLYMA_12G239200 presented significantly higher expression in crinkled leaf lines than in normal leaf lines during the V5 (fifth trifoliolate stage), R2 (full bloom stage), and R6 (full seed stage) stages. These genes were prioritized as potential prime candidates for SSCLD resistance genes. This research provides foundational data for the fine mapping of qw12-1 and cloning SSCLD-related genes, advancing our understanding of the molecular mechanisms underlying SSCLD. Full article

Background: Tessadori–Bicknell–van Haaften syndrome (OMIM #619759) is a rare autosomal dominant neurodevelopmental disorder associated with heterozygous variants in genes encoding histone H4 proteins. The condition is characterized by global developmental delay, craniofacial dysmorphism, hypotrophy, intellectual disability, and ophthalmologic anomalies. More than 30 individuals with variants in histone H4 genes have been reported to date, reflecting the genetic heterogeneity of this emerging disorder. According to OMIM, the association between the H4C11 gene and Tessadori–Bicknell–van Haaften syndrome 2 is currently considered provisional. Methods: We report the case of a 5-year-old female presenting with expressive language delay, social interaction difficulties, and craniofacial features including microcephaly, exophthalmos, and periorbital fullness (“puffy eyes”). Family history revealed two sisters with borderline intellectual functioning who have not undergone genetic testing. The patient’s father carried the same heterozygous H4C11 variant (c.97C > T), while maternal testing was negative. Results: Neuropsychological evaluation revealed borderline intellectual functioning (IQ 73 at first assessment, 85 at follow-up) with persistent expressive language impairment. Ophthalmologic examination confirmed congenital exophthalmos and hypermetropic astigmatism. Laboratory investigations showed low ferritin and mildly elevated TSH levels, which may have contributed to the observed growth delay. At follow-up, the patient showed an increase in IQ score (73 to 85); however, test–retest variability cannot be excluded. Conclusions: This case highlights the importance of careful clinical assessment and cautious interpretation of genetic findings in children with neurodevelopmental delay. Familial segregation of a variant of uncertain significance (VUS), in the absence of functional evidence, should be interpreted conservatively and integrated with detailed phenotypic evaluation to guide clinical management and follow-up. Full article

Soybean (Glycine max (L.) Merr.) is a globally important legume crop valued as a major source of plant-based protein and edible oil. Understanding the transcriptional programs underlying tissue-specific development is essential for improving seed quality and agronomic performance. Here, we present an integrative transcriptomic analysis of soybean based on 12 samples representing key seed developmental stages—including globular, heart, cotyledon, embryo, dry seed, mid-mature, and late-mature—and vegetative and reproductive tissues, including leaf, root, stem, flower bud, and seedling at 6 days after imbibition (6 DAI). Following data preprocessing and filtering, 54,880 genes were retained for downstream analysis. Principal component analysis revealed clear separation between seed and non-seed tissues, indicating that tissue identity is the dominant driver of transcriptomic variation. Analysis of the top 100 most variable genes further highlighted distinct expression modules associated with seed maturation and vegetative growth. Differential expression analysis identified 9785 genes exhibiting significant expression differences between seed and non-seed tissues, including 1139 upregulated and 8646 downregulated genes under relaxed statistical thresholds. Functional characterization of seed-upregulated genes revealed enrichment of biological processes related to storage metabolism, embryo development, and stress protection mechanisms associated with desiccation tolerance. In addition, co-expression network and correlation analyses demonstrated strong transcriptional coherence among seed tissues and distinct clustering of vegetative organs. Together, these results provide a comprehensive systems-level overview of transcriptional organization across soybean tissues and identify candidate gene sets relevant to seed biology, functional genomics, and crop improvement. Full article