Journal of Developmental Biology最新文献

{"title":"Functional and Genetic Analyses Unveil the Implication of <i>hoxa4a</i> in Zebrafish Craniofacial Development.","authors":"Le Sun, Lu Ping, Fuyu Zhang, Ruzhen Gao, Bo Zhang, Xiaowei Chen","doi":"10.3390/jdb14020022","DOIUrl":"10.3390/jdb14020022","url":null,"abstract":"<p><p>Microtia-atresia is a rare craniofacial malformation primarily affecting the first and second pharyngeal arches, leading to the deformity of the auricle and atresia of the external ear canal. Its etiology is heterogenous and largely unknown, including both genetic and environmental factors. The <i>HOXA4</i> gene has been identified as potentially pathogenetic for microtia-atresia in three twin families. A <i>hoxa4a</i> mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. <i>hoxa4a</i> was expressed in the mandible during early development in zebrafish, while the F0 mosaic knockdowns exhibited craniofacial malformations with abnormal chondrocyte morphologies. Specifically, <i>hoxa4a</i> knockdown reduced cranial neural crest cell proliferation while increasing apoptosis, markedly downregulating chondrogenic markers <i>sox9a</i> and <i>col2a1a</i>. Consequently, pharyngeal arch chondrocytes exhibited disorganized arrangement and morphological abnormalities, resulting in mandibular hypoplasia. Our findings provide important insights into the role of <i>hoxa4a</i> in zebrafish mandibular development and the pathology of microtia-atresia caused by <i>HOXA4</i> gene mutations in humans.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148031346","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":"Torpor-Induced Regulation of Poly(A) Tail Machinery in 13-Lined Ground Squirrel Brown Adipose Tissue.","authors":"Saif Rehman, William G Willmore, Kenneth B Storey","doi":"10.3390/jdb14020021","DOIUrl":"10.3390/jdb14020021","url":null,"abstract":"<p><p>The poly(A) tail has long been known to play a central role in mRNA stability, storage, and translational competence, making it a potential key regulator during hypometabolic states. During seasonal torpor, hibernating mammals must frequently enter these hypometabolic states to survive. In this study, we examined protein abundance changes in key enzymes involved in poly(A) tail synthesis, binding, and removal during torpor in the brown adipose tissue of the 13-lined ground squirrel, <i>Ictidomys tridecemlineatus</i>, using immunoblots. BAT during late torpor exhibited significantly reduced abundance of the catalytic cleavage enzyme CPSF73, but increased abundance of poly(A) polymerase PAPOLA. In contrast, poly(A)-binding proteins and major complex subunits of deadenylases, including CCR4-Not, exhibited no significant changes. Furthermore, despite unchanged levels of the translation initiation factor eIF4E, the phosphorylated variant of 4E-BP1, a potent inhibitor of the initiation factor when hypophosphorylated, was significantly reduced during late torpor. Overall, constrained mRNA maturation, preserved transcript stability, and reversible translational inhibition suggest that an important role exists for poly(A) tail regulatory machinery in hypometabolic survival throughout the torpid state.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148031326","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":"Adenosine Receptor Functionality and Desensitization Machinery in a Neuronal Cell Model of Angelman Syndrome.","authors":"Martina Contestabile, Jacqueline Fátima Martins de Almeida, Chiara De Cesari, Ilaria Tonazzini, Paolo Giovanni Artini, Simona Daniele","doi":"10.3390/jdb14020020","DOIUrl":"10.3390/jdb14020020","url":null,"abstract":"<p><p>Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of maternal UBE3A expression, leading to disrupted proteostasis and synaptic dysfunction. Adenosine is a ubiquitous neuromodulator whose G protein-coupled receptors (ARs) regulate neuronal differentiation and neurite outgrowth during development. Here, we investigated AR signaling and their influence on survival-autophagy balance and neuronal morphology in an AS cellular model. Using SH-SY5Y cells with silenced UBE3A, we found that UBE3A loss markedly decreased A1AR, A2BAR, and A3AR protein levels while significantly increasing A2AR expression. Ligand affinity was preserved across genotypes, but A1AR and A2AAR desensitization kinetics were significantly slower in UBE3A-deficient cells. These effects were associated with reduced recruitment of G protein-coupled receptor kinase 2 (GRK2) to the plasma membrane and decreased GRK2-AR association in UBE3A-deficient cells, suggesting a possible contribution of altered GRK2 dynamics to prolonged AR signaling. Functionally, A1AR and A2AR agonists preferentially promoted survival of UBE3A-deficient cells and modulated the MDM2-p53 axis and autophagy markers; A1R stimulation also increased neurite density in UBE3A-deficient cells. Together, these results identify AR-level alterations and defective desensitization machinery in AS neuronal cells and link receptor changes to downstream proteostasis and morphological phenotypes relevant to AS pathophysiology.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148031372","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":"Fetal-Fetal and Fetal-Maternal Microchimerism: Insights from Mammalian Placental Biology.","authors":"Jorge A De Los Santos Funes","doi":"10.3390/jdb14020019","DOIUrl":"10.3390/jdb14020019","url":null,"abstract":"<p><p>Feto-maternal microchimerism (Mc) refers to the exchange of cells between the fetus and mother, and fetal-fetal Mc to the exchange between fetuses during pregnancy. This phenomenon occurs across mammalian species, including humans, mice, and cattle. Key data on Mc cells and theoretical considerations regarding the presence of fetal-derived material, such as trophoblast cells, cell-free fetal DNA (cffDNA), and exosomes in maternal blood are summarized. This review aims to first, synthesize current knowledge on feto-maternal and fetal-fetal Mc across mammals, second, address three core questions: how and where Mc has been demonstrated in animals, what techniques have been used over time to detect fetal-derived material and Mc, and how placental structures influence the frequency of Mc. Finally, it aims to identify gaps in the literature for species such as horses, goats, and pigs. This article concludes that Mc is a widespread phenomenon among mammals, but detection methods and reported frequencies vary significantly by species and placental type. A biological model is presented in this article in which multinucleated trophoblast cells undergo apoptosis, releasing cffDNA that enters the maternal blood circulation after multinucleated trophoblast invasion. Advances in molecular biology technology have improved the ability to detect fetal-derived material, cells, DNA, and exosomes in maternal blood. However, notable research gaps remain for Mc in horses, goats, and pigs, highlighting the need for targeted studies to better understand species-specific patterns or a general biological model.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"14 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148031282","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":"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":"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":2.4,"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":"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":2.4,"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}

{"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":"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":2.4,"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":"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":2.4,"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":2.4,"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}

{"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":2.4,"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}