Developmental Processes Research Articles

Activation of Nrf2 at Critical Windows of Development Alters Tissue-Specific Protein S-Glutathionylation in the Zebrafish (Danio rerio) Embryo.

Activation of Nrf2-the master regulator of antioxidative response-at different stages of embryonic development has been shown to result in changes in gene expression, but the tissue-specific and downstream effects of Nrf2 activation during development remain unclear. This work seeks to elucidate the tissue-specific Nrf2 cellular localization and the downstream changes in protein S-glutathionylation during critical windows of zebrafish (Danio rerio) development. Wild-type and mutant zebrafish embryos with a loss-of-function mutation in Nrf2a were treated with two canonical activators, sulforaphane (SFN; 40 µM) or tert-butylhydroquinone (tBHQ; 1 µM), for 6 h at either pharyngula, hatching, or the protruding-mouth stage. Nrf2a protein and S-glutathionylation were visualized in situ using immunohistochemistry. At the hatching stage, Nrf2a protein levels were decreased with SFN, but not tBHQ, exposure. Exposure to both activators, however, decreased downstream S-glutathionylation. Stage- and tissue-specific differences in Nrf2a protein and S-glutathionylation were identified in the pancreatic islet and liver. Protein S-glutathionylation in Nrf2a mutant fish was increased in the liver by both activators, but not the islets, indicating a tissue-specific and Nrf2a-dependent dysregulation. This work demonstrates that critical windows of exposure and Nrf2a activity may influence redox homeostasis and highlights the importance of considering tissue-specific outcomes and sensitivity in developmental redox biology.

Global research trends and hotspots in overweight/obese comorbid with depression among children and adolescents: A bibliometric analysis.

Overweight/obesity combined with depression among children and adolescents (ODCA) is a global concern. The bidirectional relationship between depression and overweight/obesity often leads to their comorbidity. Childhood and adolescence represent critical periods for physical and psychological development, during which the comorbidity of overweight/obesity and depression may increase the risk of adverse health outcomes. To evaluate the relationship between ODCA, we conduct a bibliometric analysis to aid in formulating prevention and treatment strategies. From 2004 to 2023, articles related to ODCA were selected using the Science Citation Index Expanded from the Web of Science Core Collection. Bibliometric analysis of relevant publications, including countries/regions, institutions, authors, journals, references, and keywords, was conducted using the online bibliometric analysis platforms, CiteSpace, VOSviewer, and bibliometrix. Between 2004 and 2023, a total of 1573 articles were published on ODCA. The United States has made leading contributions in this field, with Harvard University emerging as the leading contributor in terms of research output, and Tanofsky being the most prolific author. The J Adolescent Health has shown significant activity in this domain. Based on the results of the keyword and reference analyses, inequality, adverse childhood experiences, and comorbidities have become hot topics in ODCA. Moreover, the impact of balanced-related behavior and exploration of the biological mechanisms, including the potential role of key adipocytokines and lipokines, as well as inflammation in ODCA, have emerged as frontier topics. The trend of a significant increase in ODCA publications is expected to continue. The research findings will contribute to elucidating the pathogenic mechanisms of ODCA and its prevention and treatment.

Uncovering developmental diversity in the field.

Many developmental biologists seldom leave the lab for research, relying instead on establishing colonies of traditional and emerging model systems. However, to fully understand the mechanisms and principles of development and evolution, including the role of ecology and the environment, it is important to study a diverse range of organisms in context. In this Perspective, we hear from five research teams from around the world about the importance and challenges of going into the field to study their organisms of interest. We also invite you to share your own fieldwork stories on the Node.

Tissue-scale in vitro epithelial wrinkling and wrinkle-to-fold transition

Although epithelial folding is commonly studied using in vivo animal models, such models exhibit critical limitations in terms of real-time observation and independent control of experimental parameters. Here, we develop a tissue-scale in vitro epithelial bilayer folding model that incorporates an epithelium and extracellular matrix (ECM) hydrogel, thereby emulating various folding structures found in in vivo epithelial tissue. Beyond mere folding, our in vitro model realizes a hierarchical transition in the epithelial bilayer, shifting from periodic wrinkles to a single deep fold under compression. Experimental and theoretical investigations of the in vitro model imply that both the strain-stiffening of epithelium and the poroelasticity of ECM influence the folded structures of epithelial tissue. The proposed in vitro model will aid in investigating the underlying mechanism of tissue-scale in vivo epithelial folding relevant to developmental biology and tissue engineering.

Is auxin the key to improve crop nitrogen use efficiency for greener agriculture?

Strengthening future food security through the application of unsustainable levels of inorganic nitrogen (N) fertilizers to crop fields may exacerbate environmental damage. Coordination of N-use efficiency (NUE) and plant growth is, therefore, crucial for sustainable agriculture. Auxin plays pivotal roles in developmental and signaling responses that affect NUE. Hence, a better understanding of these processes provides great potential to improve crop NUE. This review summarizes the effects of auxin on N-related and root developmental processes that either directly or indirectly affect NUE in the model plant Arabidopsis and major crop species to highlight the potential of fostering sustainable agricultural development in the future through modulating auxin-related processes.

Suppressing a β-1,3-glucanase gene expression increases the seed and fibre yield in cotton.

Seeds are initiated from the carpel margin meristem (CMM) and high seed yield is top one of breeding objectives for many crops. β-1,3-glucanases play various roles in plant growth and developmental processes; however, whether it participates in CMM development and seed formation remains largely unknown. Here, we identified a β-1,3-glucanase gene (GLU19) as a determinant of CMM callose deposition and seed yield in cotton. GLU19 was differentially expressed in carpel tissues between Gossypium barbadense (Gb) and Gossypium hirsutum (Gh). Based on resequencing data, one interspecies-specific InDel in the promoter of GLU19 was further detected. The InDel was involved in the binding site of the CRABS CLAW (CRC) transcription factor, a regulator of carpel development. We found that the CRC binding affinity to the GLU19 promoter of G. barbadense was higher than that of G. hirsutum. Since G. barbadense yields fewer seeds than G. hirsutum, we speculated that stronger CRC binding to the GLU19 promoter activated higher expression of GLU19 which in turn suppressed seed production. Consistent with this hypothesis was that the overexpression of GhGLU19 caused reduced seed number, boll weight and less callose formation in CMM. Conversely, GhGLU19-knockdown (GhGLU19-KD) cotton led to the opposite phenotypes. By crossing GhGLU19-KD lines with several G. hirsutum and G. barbadense cotton accessions, all F1 and F2 plants carrying GhGLU19-KD transgenic loci exhibited higher seed yield than control plants without the locus. The increased seed effect was also found in the down-regulation of Arabidopsis orthologs lines, indicating that this engineering strategy may improve the seed yield in other crops.

A case report on congenital hypothyroidism and alpha thalassemia in children with anemia and muscle damage as the main manifestation.

This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. The child was diagnosed with CH with alpha thalassemia. The patient was treated with levothyroxine sodium and anemia correction. The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.

The Key Targets of NO-Mediated Post-Translation Modification (PTM) Highlighting the Dynamic Metabolism of ROS and RNS in Peroxisomes.

Nitric oxide (NO) has been firmly established as a key signaling molecule in plants, playing a significant role in regulating growth, development and stress responses. Given the imperative of sustainable agriculture and the urgent need to meet the escalating global demand for food, it is imperative to safeguard crop plants from the effects of climate fluctuations. Plants respond to environmental challenges by producing redox molecules, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), which regulate cellular, physiological, and molecular processes. Nitric oxide (NO) plays a crucial role in plant stress tolerance, acting as a signaling molecule or free radical. NO is involved in various developmental processes in plants through diverse mechanisms. Exogenous NO supplementation can alleviate the toxicity of abiotic stresses and enhance plant resistance. In this review we summarize the studies regarding the production of NO in peroxisomes, and how its molecule and its derived products, (ONOO-) and S-nitrosoglutathione (GSNO) affect ROS metabolism in peroxisomes. Peroxisomal antioxidant enzymes including catalase (CAT), are key targets of NO-mediated post-translational modification (PTM) highlighting the dynamic metabolism of ROS and RNS in peroxisomes.

Gene Expression Profile Identifies LncRNA AL355974.3 As a Potential Glioma Biomarker.

Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients. First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes. Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.

Molecular Developmental Biology of Fibrodysplasia Ossificans Progressiva: Measuring the Giant by Its Toe.

When a genetic disease is characterized by the abnormal activation of normal molecular pathways and cellular events, it is illuminating to critically examine the places and times of these activities both in health and disease. Therefore, because heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP) is by far the disease's most prominent symptom, attention is also directed toward the pathways and processes of bone formation during skeletal development. FOP is recognizable by effects of the causative mutation on skeletal development even before HO manifests, specifically in the malformation of the great toes. This signature skeletal phenotype is the most highly penetrant, but is only one among several skeletal abnormalities associated with FOP. Patients may present clinically with joint malformation and ankylosis, particularly in the cervical spine and costovertebral joints, as well as characteristic facial features and a litany of less common, non-skeletal symptoms, all stemming from missense mutations in the ACVR1 gene. In the same way that studying the genetic cause of HO advanced our understanding of HO initiation and progression, insight into the roles of ACVR1 signaling during tissue development, particularly in the musculoskeletal system, can be gained from examining altered skeletal development in individuals with FOP. This review will detail what is known about the molecular mechanisms of developmental phenotypes in FOP and the early role of ACVR1 in skeletal patterning and growth, as well as highlight how better understanding these processes may serve to advance patient care, assessments of patient outcomes, and the fields of bone and joint biology.

R2R3-MYB Gene Family in Coptis teeta Wall.: Genome-Wide Identification, Phylogeny, Evolutionary Expansion, and Expression Analyses during Floral Development.

The R2R3-MYB gene family represents a widely distributed class of plant transcription factors. This gene family plays an important role in many aspects of plant growth and development. However, the characterization of R2R3-MYB genes present in the genome of Coptis teeta has not been reported. Here, we describe the bioinformatic identification and characterization of 88 R2R3-MYB genes in this species, and the identification of members of the R2R3-MYB gene family in species within the order Ranales most closely related to Coptis teeta. The CteR2R3-MYB genes were shown to exhibit a higher degree of conservation compared to those of A. thaliana, as evidenced by phylogeny, conserved motifs, gene structure, and replication event analyses. Cis-acting element analysis confirmed the involvement of CteR2R3-MYB genes in a variety of developmental processes, including growth, cell differentiation, and reproduction mediated by hormone synthesis. In addition, through homology comparisons with the equivalent gene family in A. thaliana, protein regulatory network prediction and transcriptome data analysis of floral organs across three time periods of flower development, 17 candidate genes were shown to exhibit biased expression in two floral phenotypes of C. teeta. This suggests their potential involvement in floral development (anther development) in this species.

The eukaryotic translation initiation factor eIF4E regulates flowering and circadian rhythm in Arabidopsis.

Translation initiation is a critical, rate-limiting step in protein synthesis. The eukaryotic translation initiation factor 4E (eIF4E) plays an essential role in this process. However, the mechanisms by which eIF4E-dependent translation initiation regulates plant growth and development remain not fully understood. In this study, we found that Arabidopsis eIF4E proteins are distributed in both the nucleus and cytoplasm, with only the cytoplasmic eIF4E being involved in the control of photoperiodic flowering. Genome-wide translation profiling using Ribo-tag sequencing reveals that eIF4E may regulate plant flowering by maintaining the homeostatic translation of components in the photoperiodic flowering pathway. eIF4E not only regulates the translation of flowering genes such as FLOWERING LOCUS T (FT) and FLOWERING LOCUS D (FLD) but also influences the translation of circadian genes like CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and PSEUDO-RESPONSE REGULATOR 9 (PRR9). Consistently, our results show that the eIF4E modulates the rhythmic oscillation of the circadian clock. Together, our study provides mechanistic insights into how the protein translation regulates multiple developmental processes in Arabidopsis, including the circadian clock and photoperiodic flowering.

Vitamin D Sufficiency and Its Relationship with Indicators of Physical Development and the State of Bone Tissue in Cadets of a Military Higher Educational Institution

Vitamin D Sufficiency and Its Relationship with Indicators of Physical Development and the State of Bone Tissue in Cadets of a Military Higher Educational Institution

Cognitive dysfunction following brain trauma results from sex-specific reactivation of the developmental pruning processes.

Cognitive losses resulting from severe brain trauma have long been associated with the focal region of tissue damage, leading to devastating functional impairment. For decades, researchers have focused on the sequelae of cellular alterations that exist within the perilesional tissues; however, few clinical trials have been successful. Here, we employed a mouse brain injury model that resulted in expansive synaptic damage to regions outside the focal injury. Our findings demonstrate that synaptic damage results from the prolonged increase in D-serine release from activated microglia and astrocytes, which leads to hyperactivation of perisynaptic NMDARs, tagging of damaged synapses by complement components, and the reactivation of developmental pruning processes. We show that this mechanistic pathway is reversible at several stages within a prolonged and progressive period of synaptic loss. Importantly, these key factors are present in acutely injured brain tissue acquired from patients with brain injury, which supports a therapeutic neuroprotective strategy.

Comprehensive network modeling approaches unravel dynamic enhancer-promoter interactions across neural differentiation

BackgroundIncreasing evidence suggests that a substantial proportion of disease-associated mutations occur in enhancers, regions of non-coding DNA essential to gene regulation. Understanding the structures and mechanisms of the regulatory programs this variation affects can shed light on the apparatuses of human diseases.ResultsWe collect epigenetic and gene expression datasets from seven early time points during neural differentiation. Focusing on this model system, we construct networks of enhancer-promoter interactions, each at an individual stage of neural induction. These networks serve as the base for a rich series of analyses, through which we demonstrate their temporal dynamics and enrichment for various disease-associated variants. We apply the Girvan-Newman clustering algorithm to these networks to reveal biologically relevant substructures of regulation. Additionally, we demonstrate methods to validate predicted enhancer-promoter interactions using transcription factor overexpression and massively parallel reporter assays.ConclusionsOur findings suggest a generalizable framework for exploring gene regulatory programs and their dynamics across developmental processes; this includes a comprehensive approach to studying the effects of disease-associated variation on transcriptional networks. The techniques applied to our networks have been published alongside our findings as a computational tool, E-P-INAnalyzer. Our procedure can be utilized across different cellular contexts and disorders.

Repetitive Sequence Stability in Embryonic Stem Cells.

Repetitive sequences play an indispensable role in gene expression, transcriptional regulation, and chromosome arrangements through trans and cis regulation. In this review, focusing on recent advances, we summarize the epigenetic regulatory mechanisms of repetitive sequences in embryonic stem cells. We aim to bridge the knowledge gap by discussing DNA damage repair pathway choices on repetitive sequences and summarizing the significance of chromatin organization on repetitive sequences in response to DNA damage. By consolidating these insights, we underscore the critical relationship between the stability of repetitive sequences and early embryonic development, seeking to provide a deeper understanding of repetitive sequence stability and setting the stage for further research and potential therapeutic strategies in developmental biology and regenerative medicine.

Understanding regional structure through spatial networks: A simulation optimization framework for exploring balanced development

The spatial structure inherently reflects a region's pattern and developmental processes. Understanding the rationality behind this structure and identifying optimization directions are pivotal for macro-level regulation of regional development and collaborative efforts. This study initiates a discussion on the composition and optimization mechanisms inherent in spatial structures. Adopting a spatial network perspective, we interpret the interaction dynamics within regional morphological structures as the consumption of resources through flows. We transform structural optimization into an equilibrium matching process of resources and establish a quantitative research framework that integrates network modeling, structural issue identification, and optimization strategies. Then, we selected the Guangdong-Hong Kong-Macao Greater Bay Area as our empirical subject, and obtained three important results: (1) Before optimization, we identified structural spatial imbalance characteristics; (2) We explored the evolutionary trend of optimization and delineated four main optimization stages; (3) The spatial structure of the region was improved, and significant benefits in equilibrium and resource utilization was achieved. Finally, we discussed the feasibility of the framework and the necessity to integrate policy networks, hoping to assist regional managers in macro-governance and enhance the rationality of regional planning and coordination.

Inhibitory systems in brain evolution: pathways of vulnerability in neurodevelopmental disorders.

The evolution of the primate brain has been characterized by the reorganization of key structures and circuits underlying derived specializations in sensory systems, as well as social behavior and cognition. Among these, expansion and elaboration of the prefrontal cortex has been accompanied by alterations to the connectivity and organization of subcortical structures, including the striatum and amygdala, underlying advanced aspects of executive function, inhibitory behavioral control, and socioemotional cognition seen in our lineages. At the cellular level, the primate brain has further seen an increase in the diversity and number of inhibitory GABAergic interneurons. A prevailing hypothesis holds that disruptions in the balance of excitatory to inhibitory activity in the brain underlies the pathophysiology of many neurodevelopmental and psychiatric disorders. This review highlights the evolution of inhibitory brain systems and circuits, and suggests that recent evolutionary modifications to GABAergic circuitry may provide the substrate for vulnerability to aberrant neurodevelopment. We further discuss how modifications to primate and human social organization and life history may shape brain development in ways that contribute to neurodivergence and the origins of neurodevelopmental disorders. Many brain systems have seen functional reorganization in the mammalian, primate, and human brain. Alterations to inhibitory circuitry in frontostriatal and frontoamygdalar systems support changes in social behavior and cognition. Increased complexity of inhibitory systems may underlie vulnerabilities to neurodevelopmental and psychiatric disorders, including autism and schizophrenia. Changes observed in Williams syndrome may further elucidate the mechanisms by which alterations in inhibitory systems lead to changes in behavior and cognition. Developmental processes, including altered neuroimmune function and age-related vulnerability of inhibitory cells and synapses, may lead to worsening symptomatology in neurodevelopmental and psychiatric disorders.

Transcriptome Analysis Reveals the Regulatory Mechanism of Lipid Metabolism and Oxidative Stress in Litopenaeus vannamei under Low-Salinity Stress

Salinity is a crucial environmental factor influencing the survival, growth, development, and reproduction of aquatic animals. However, the underlying molecular mechanisms of the shrimp’s response to salinity stress are not yet fully understood. Therefore, we used the Illumina NovaSeq 6000 platform to perform transcriptome sequencing of the hepatopancreas of Litopenaeus vannamei under high-salinity (30 PSU), medium-salinity (10 PSU), and low-salinity (0.5 PSU) conditions. We obtained 63.23 Gb of high-quality data and identified 3589 differentially expressed genes (DEGs), including 1638 upregulated and 1951 downregulated genes. Notably, a comparison between the control group (30 PSU) and the low-salinity group (0.5 PSU) revealed that the BBOX1 and CHE1 genes were significantly upregulated, while the ACOX1, MPV, CYP2L1, GCH, MVK, TREt1, and XDH genes were significantly downregulated. These genes are primarily involved in key metabolic pathways, such as fatty acid oxidation, cholesterol metabolism, and hormone synthesis and metabolism. The key genes involved in fatty acid β-oxidation, such as ACOX1, ACAD, HADH, HSD17B4, PECR, CROT, PIPOX, and CG5009, all showed a downward trend, suggesting that L. vannamei may respond to salt stress by regulating fatty acid oxidative metabolism, optimizing energy utilization, and maintaining cell homeostasis under low-salinity conditions. Functional annotation of gene ontology (GO) and KEGG pathway enrichment analysis highlighted the roles of these significant DEGs in the adaptation of L. vannamei to environments of varying salinity, underscoring the importance of metabolic pathways in their adaptive physiological responses. This study provides a crucial molecular biological basis for understanding the molecular mechanisms and physiological protection strategies of L. vannamei under salinity stress.

Plasmodesmata Function and Callose Deposition in Plant Disease Defense.

Callose, found in the cell walls of higher plants such as β-1,3-glucan with β-1,6 branches, is pivotal for both plant development and responses to biotic and abiotic stressors. Plasmodesmata (PD), membranous channels linking the cytoplasm, plasma membrane, and endoplasmic reticulum of adjacent cells, facilitate molecular transport, crucial for developmental and physiological processes. The regulation of both the structural and transport functions of PD is intricate. The accumulation of callose in the PD neck is particularly significant for the regulation of PD permeability. This callose deposition, occurring at a specific site of pathogenic incursion, decelerates the invasion and proliferation of pathogens by reducing the PD pore size. Scholarly investigations over the past two decades have illuminated pathogen-induced callose deposition and the ensuing PD regulation. This gradual understanding reveals the complex regulatory interactions governing defense-related callose accumulation and protein-mediated PD regulation, underscoring its role in plant defense. This review systematically outlines callose accumulation mechanisms and enzymatic regulation in plant defense and discusses PD's varied participation against viral, fungal, and bacterial infestations. It scrutinizes callose-induced structural changes in PD, highlighting their implications for plant immunity. This review emphasizes dynamic callose calibration in PD constrictions and elucidates the implications and potential challenges of this intricate defense mechanism, integral to the plant's immune system.