Ann-Kathrin Schmitt, Victoria Tjora, Nela Kelam, Marija Jurić Gunjača, Petar Todorović, Clelia Picard, Manel Loche-Dalmon, Katarina Vukojević, Anita Racetin
{"title":"Melatonin Receptor 1 and Melatonin Receptor 2 Expression During Human Kidney Development and Their Association with CAKUT.","authors":"Ann-Kathrin Schmitt, Victoria Tjora, Nela Kelam, Marija Jurić Gunjača, Petar Todorović, Clelia Picard, Manel Loche-Dalmon, Katarina Vukojević, Anita Racetin","doi":"10.3390/jdb14020018","DOIUrl":"https://doi.org/10.3390/jdb14020018","url":null,"abstract":"<p><strong>Background/objectives: </strong>Growing evidence indicates that melatonin contributes to kidney development and function, while disruptions of fetal circadian signaling have been linked to congenital anomalies of the kidney and urinary tract (CAKUT). This study aimed to characterize the developmental and spatial expression patterns of melatonin receptors MTNR1A and MTNR1B in normal human fetal kidneys and in CAKUT phenotypes.</p><p><strong>Methods: </strong>This study analyzed 40 human fetal kidney specimens, including healthy controls and CAKUT cases (horseshoe kidneys, duplex kidneys, and dysplastic kidneys), obtained from spontaneous abortions and pregnancy terminations. Samples were classified into developmental phases Ph2-Ph4 according to established morphological criteria. Immunofluorescence staining was used to visualize MTNR1A and MTNR1B expression. Quantitative analysis was performed using ImageJ, measuring the fluorescence area percentage. Statistical comparisons were conducted using a two-way ANOVA.</p><p><strong>Results: </strong>In control kidneys, MTNR1A expression was predominantly observed in glomeruli and interstitial cells and showed a descending trend across developmental stages, whereas MTNR1B was localized to glomeruli and strongly to the apical membranes of tubules, particularly distal tubules, without substantial developmental variation. CAKUT phenotypes exhibited higher expression of both receptors compared to controls. Significant phase-dependent differences in MTNR1A expression were observed in horseshoe, duplex, and dysplastic kidneys. MTNR1B expression decreased across developmental stages in dysplastic kidneys and differed significantly between Ph3 and Ph4 in duplex kidneys. At Ph3, duplex kidneys showed the highest MTNR1B expression.</p><p><strong>Conclusions: </strong>Altered developmental expression patterns of MTNR1A and MTNR1B in CAKUT suggest an association between melatonin signaling and abnormal human kidney development.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel Functions and Potential of Ribosomes: From Cellular Transdifferentiation to Applications in Cell-Cultured Foods.","authors":"Shota Inoue, Hiroaki Hatano, Ikko Kawashima, Kunimasa Ohta","doi":"10.3390/jdb14020017","DOIUrl":"https://doi.org/10.3390/jdb14020017","url":null,"abstract":"<p><p>Ribosomes are widely recognized as large intracellular macromolecular complexes responsible for protein synthesis. However, in recent years, numerous studies have revealed that ribosomal proteins possess non-canonical functions beyond translation, including roles in cell fate regulation, development, and disease. This review outlines emerging concepts surrounding the extracellular functions of ribosomes, with a particular focus on ribosome-induced cellular plasticity and transdifferentiation. Our studies have demonstrated that the incorporation of exogenous ribosomes reprograms somatic cells into a multipotent state and promotes differentiation into multiple lineages. These findings represent an alternative perspective to the conventional view of ribosomes as merely translational components. Furthermore, we discuss the biological significance of factors secreted by ribosome-incorporated cells by integrating the paracrine hypothesis with ribosome-mediated cell fate conversion. Finally, we explore the potential applications of ribosomes in regenerative medicine and cell-cultured food production. By redefining ribosomes as active regulators of cellular identity, this review provides a conceptual framework for understanding ribosome-driven cell fate regulation and its potential applications in sustainable biotechnology.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bing Jia, Mohamed Milad, Hannah C Boehler, Adam Guerra, Joshua Mowry, Jessica Hiley, James Kasen Lisonbee, Michael Hafen, Troy Camarata
{"title":"Conserved Metanephric Kidney Development and Genome Methylation in Red-Eared Slider Turtle (<i>Trachemys scripta elegans</i>).","authors":"Bing Jia, Mohamed Milad, Hannah C Boehler, Adam Guerra, Joshua Mowry, Jessica Hiley, James Kasen Lisonbee, Michael Hafen, Troy Camarata","doi":"10.3390/jdb14020016","DOIUrl":"https://doi.org/10.3390/jdb14020016","url":null,"abstract":"<p><p>Mammals and reptiles possess a metanephric kidney as the terminal renal organ for homeostasis of solutes and waste products. The development of the metanephric kidney has primarily been studied in mammalian model systems. Little is known about the conservation of metanephric kidney formation in non-mammalian species such as reptiles. Uniquely, reptiles maintain kidney progenitor cell populations throughout life and continually develop new nephrons, the functional unit of the kidney. The red-eared slider turtle, <i>Trachemys scripta elegans</i>, was utilized to investigate the conservation of reptilian metanephric kidney development. The nephron progenitor cell (NPC) marker, Six2, was detected in whole-mount turtle kidneys in a similar pattern to mammals. However, there were differences in progenitor cell niche morphology where turtle NPC populations formed distinct elongated rows instead of the rosette-like morphology found in the mouse. The pattern of NPC populations in the embryonic turtle kidney was maintained in the adult turtle. Whole-genome bisulfite sequencing was performed on cortical tissue containing the NPC populations from adult turtle kidneys and compared to those of adult mice. Significant conservation of gene methylation was detected in adult cortical tissue between the two species, although unique signatures were detected in turtle samples related to DNA repair and β-catenin signaling. This suggests a high level of conservation of metanephric kidney development at the genetic level.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Compensatory Serotonin Synthesis and Histone H3 Serotonylation in Preimplantation Embryos Exposed to Maternal Fluoxetine or Monoamine Oxidase Blockade.","authors":"Veronika S Frolova, Denis A Nikishin","doi":"10.3390/jdb14020015","DOIUrl":"https://doi.org/10.3390/jdb14020015","url":null,"abstract":"<p><p>Serotonin is a critical morphogen in early development, yet the mechanisms regulating its homeostasis in the preimplantation embryo remain unclear, particularly under conditions of maternal antidepressant exposure. Here, we investigated embryonic serotonergic autonomy using mouse models of pharmacological transport blockade (maternal fluoxetine treatment) and in vitro treatment with the monoamine oxidase inhibitor pargyline. We employed immunofluorescence, RT-qPCR, and live-cell imaging to assess metabolic flux, gene expression, and physiological health. We demonstrate that monoamine oxidase functions as a metabolic firewall, progressively maturing from zygote to blastocyst to degrade excess amines. Paradoxically, maternal serotonin transporter blockade triggered significant intracellular serotonin hyper-accumulation in blastocysts, associated with a trend toward a compensatory upregulation of the biosynthetic gene <i>Ddc</i>. While this serotonin overload did not compromise morphology, mitochondrial function, or pluripotency marker expression, it induced a robust epigenetic response. Excess serotonin promoted elevated H3Q5ser immunoreactivity in both nuclear and cytoplasmic compartments via a transglutaminase-dependent mechanism. These findings reveal that the preimplantation embryo possesses a resilient, autonomous serotonergic system capable of compensatory synthesis. However, environmental fluctuations are chemically recorded via transglutaminase-mediated serotonylation, representing an epigenetic mark that warrants further long-term study within the Developmental Origins of Health and Disease (DOHaD) framework.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transformation of the Biological Paradigm in Bone Regeneration: An Integrative Review.","authors":"Diyana Vladova","doi":"10.3390/jdb14010014","DOIUrl":"10.3390/jdb14010014","url":null,"abstract":"<p><p>Bone tissue is among the most commonly transplanted tissues worldwide. The treatment of critical-sized bone defects remains a significant challenge, as there is currently no universally accepted experimental model or therapeutic standard. Recent advances in fundamental cell biology are driving a paradigm shift in approaches to bone regeneration, highlighting the transformative potential of biofabrication technologies that integrate tissue engineering with personalized regenerative strategies. Three-dimensional (3D) bioprinting technology enables precise control over the architecture and spatial distribution of cellular and biologically active components, facilitating the creation of complex, personalized bone constructs. Central to this process are bioinks and biomaterials that mimic the extracellular matrix (ECM) and provide an optimal microenvironment for cellular function. Despite the substantial body of accumulated data, a comprehensive theoretical framework for functional bone biofabrication has not yet been fully established, emphasizing both the challenges and the innovative potential of the field. This integrative review synthesizes current knowledge on bone biology-from embryogenesis and cell-matrix interactions to molecular and neural regulation-and links it to the opportunities offered by biofabrication. Particular attention is given to bioinks as mediators between cell biology and engineering sciences, as well as to strategies for creating biomimetic ECM, optimizing scaffold design, and guiding future research toward clinically translatable bone regeneration.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13027023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Beatriz Matos, Laura Jesus Castro, Torcato Martins
{"title":"SIX3 as a Regulator of Development and Disease.","authors":"Ana Beatriz Matos, Laura Jesus Castro, Torcato Martins","doi":"10.3390/jdb14010013","DOIUrl":"10.3390/jdb14010013","url":null,"abstract":"<p><p>Transcriptional regulation is pivotal for developmental processes and cell fate specification in homeostasis. One particularly relevant group of transcription factors is the sine oculis homeobox (SIX) family, which is involved in a wide range of molecular processes from development to tissue maintenance. Within this family, distinct subfamilies exhibit specific DNA-binding preferences and can function as transcriptional activators or repressors. In this review, we focus on the Optix/SIX3-SIX6 subfamily and discuss their roles as transcriptional regulators, as well as the consequences of their deregulation for neuronal and ocular development and for the maintenance of tissue homeostasis. We further examine how SIX3 can act either as a tumour suppressor or as a marker of poor prognosis in different cancer types. Moreover, we summarize recent findings on the role of SIX3 in pancreatic β cells and highlight emerging evidence that SIX2 also contributes to β-cell identity and regulatory stability. Downregulation of SIX2 and SIX3 alters gene regulatory programs associated with β-cell homeostasis and contributes to type 2 diabetes. As accumulating evidence links members of the SIX family to cancer and metabolic disease, it is crucial to characterize how these transcription factors regulate cell identity, with important implications for disease mechanisms and therapeutic strategies.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13026914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic Impacts of Biological Exposures.","authors":"Amalia S Parra, Christopher A Johnston","doi":"10.3390/jdb14010012","DOIUrl":"10.3390/jdb14010012","url":null,"abstract":"<p><p>Development and maintenance of complex tissues depends on a number of coordinated steps from early development through adulthood. These processes are fundamentally controlled by highly regulated gene expression patterns. Although critical contributors during development, intrinsic changes in gene expression alone cannot fully explain the complicated pathways that control tissue homeostasis. Rather, tissues are continuously exposed to extrinsic factors that also influence essential cellular processes. These external environmental factors are collectively known as the exposome. Notably, how different exposures impact gene expression and protein function, as well as how certain exposures lead to disease states, is not well understood. To understand how internal and external factors influence organismal development and homeostasis, it is necessary to consider how genetic and nongenetic components interact to direct critical biochemical pathways. Doing so presents new avenues for precision medicine, understanding disease progression, identifying biological threats, and improving biological security concerns. In this review, we present recent advances in exposure biology, focusing on how these innovations can help identify novel biomarkers to better understand changing exposome components. We also discuss the need to integrate technologies and exposure research to better identify and predict threats.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13028019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Origins of Avian Hyperactive Mitochondria, Genome Compaction, and Air-Sac Physiology in Early Theropods During the Carnian Pluvial Episode.","authors":"Takumi Satoh","doi":"10.3390/jdb14010011","DOIUrl":"10.3390/jdb14010011","url":null,"abstract":"<p><p>Extant birds and the earliest dinosaurs may share fundamental metabolic features essential for aerobic exercise, suggesting that the extraordinary physical performance typical of avian species originated when dinosaurs first appeared during the Carnian Pluvial Episode (CPE). This physiological adaptation is complemented by hyperactive mitochondria that exhibit high oxygen consumption and low reactive oxygen species production. Molecular genomics of fossils, the so-called \"Jurassic Genome,\" indicates that these early dinosaurs possessed compact genomes, 50-60% the size of the human genome, and small cells, implying a highly stringent metabolic regime. We suggest that hyperactive mitochondria, closely associated with compact genomes and small cells, drive theropod adaptation to the hot, dry, and hypoxic environments of the Late Triassic period, ultimately enabling their ecological dominance. Early dinosaurs such as Herrerasaurus are hypothesized to have possessed advanced physiological traits shared with modern birds, including hyperactive mitochondria, compact genomes, small cells, and a developing air-sac system. Collectively, these features most likely may have contributed to exceptional metabolic capacity, locomotor performance, and adaptation to the harsh environment of the CPE.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13026812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolutionary Restructuring and Systematic Review of the <i>NBPF Gene Family</i>: Comparative Genomics, Functional Divergence, and Disease-Linked Pathways.","authors":"Manuel Escalona, Rosa Roy","doi":"10.3390/jdb14010010","DOIUrl":"10.3390/jdb14010010","url":null,"abstract":"<p><p>The Neuroblastoma Breakpoint Family (NBPF) consists of 23 genes, 9 of which are pseudogenes, and is characterized by extensive duplication events and species-specific diversification in <i>Homo sapiens</i>, as well as by the presence of a unique protein domain known as Olduvai (also referred to as DUF1220 or the NBPF domain). Previous studies have attempted to define subfamilies based on the presence of HLS triplet domains; however, this classification has become increasingly unclear with the identification of additional <i>NBPF</i> members. The family remains poorly understood, and the functions of many genes are still unknown, although several have been hypothesized to play key roles in cell proliferation and developmental processes, particularly in neural and skeletal tissues. In this study, we systematically analyzed all available data on the <i>NBPF</i> gene family using the PRISMA-S methodology to infer the biological functions in which these genes may be involved. We also generated multiple phylogenetic trees to support the creation of coherent subfamilies and to correlate the origin of each subfamily with homologous genes in our last common ancestor with the <i>Pan</i> genus, providing what we believe to be one of the most comprehensive phylogenetic reconstructions including all currently annotated NBPF members. Through comparative genomic and phylogenetic analyses, we propose that the <i>NBPF</i> may have originated from a duplication of the <i>PDE4DIP</i> gene, with <i>NBPF26</i> representing the ancestral member from which the remaining NBPF genes diverged via lineage-specific segmental duplications. In this systematic review and comparative genomic study, we present the first integrative synthesis of our knowledge of the <i>NBPF</i>, encompassing its evolutionary origins, structural dynamics, expression across tissues, and clinical associations.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13028154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Influence of Fluidic Flow Stress on the Development of the Secondary Palate.","authors":"Masayo Nagata, Satoru Hayano, Ziyi Wang, Takahiro Kosami, Hiroshi Kamioka","doi":"10.3390/jdb14010009","DOIUrl":"10.3390/jdb14010009","url":null,"abstract":"<p><p>Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and β-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/β-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}