Saai Suryanarayanan , Dawn S. Chen , Yamei Zuo , Elizabeth J. Gleason , Zhaorong Zhu , Steven W. L'Hernault , Amber Krauchunas , Andrew Singson
{"title":"The Caenorhabditis elegans spe-21 gene that encodes a palmitoyltransferase is necessary for spermiogenesis","authors":"Saai Suryanarayanan , Dawn S. Chen , Yamei Zuo , Elizabeth J. Gleason , Zhaorong Zhu , Steven W. L'Hernault , Amber Krauchunas , Andrew Singson","doi":"10.1016/j.ydbio.2025.08.003","DOIUrl":"10.1016/j.ydbio.2025.08.003","url":null,"abstract":"<div><div>In most animals, spermatids that are produced must further differentiate into fertilization-competent spermatozoa after completing meiosis. In <em>Caenorhabditis elegans</em>, this process is known as spermiogenesis or spermatid activation and it results in the transformation of round, non-motile spermatids into amoeboid, motile spermatozoa. Spermatid activation in <em>C. elegans</em> is also associated with the fusion of Golgi-derived vesicles called the <u>m</u>embranous <u>o</u>rganelles (MOs) with the plasma membrane. This fusion process is required for producing a fertilization-competent surface on the sperm by placing MO-carried, resident proteins onto the spermatozoon membrane. We have identified, cloned, and characterized the role of <em>spe-21</em>, also designated as <em>dhhc-5,</em> during both hermaphrodite and male spermatid activation. Putative <em>spe-21</em> null mutant worms are severely sub-fertile at all studied growth temperatures. <em>spe-21</em> mutant spermatids fail to activate either <em>in vivo</em> or <em>in vitro</em> after treatment with known chemical activators. We have found that <em>spe-21</em> is necessary for MO fusion and pseudopod formation in spermatids. The <em>spe-21</em> gene encodes a predicted four pass transmembrane protein with a conserved Asp-His-His-Cys (DHHC) tetrapeptide zinc finger motif embedded in a cysteine rich region (DHHC-CRD type zinc finger motif). Generally, proteins with DHHC-CRD motifs catalyze the post-translational addition of palmitate to their protein substrates and are called palmitoyltransferases or <u>p</u>almitoyl<u>a</u>cyl<u>t</u>ransferases (PATs). We also found that mNeonGreen-tagged SPE-21 localizes to the MOs in spermatids. Together, our findings show that SPE-21 is an MO localized palmitoyltransferase required for proper spermatid activation and creation of fertilization-competent spermatozoa.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 77-90"},"PeriodicalIF":2.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yunus H. Ozekin, Rebecca O'Rourke, Emily Anne Bates
{"title":"Kcnj2 regulates electrical activity-induced gene networks in embryonic mouse palate shelves","authors":"Yunus H. Ozekin, Rebecca O'Rourke, Emily Anne Bates","doi":"10.1016/j.ydbio.2025.07.019","DOIUrl":"10.1016/j.ydbio.2025.07.019","url":null,"abstract":"<div><div>Cleft palate interferes with eating, drinking, breathing, and speech, causing significant human suffering. Fetal exposure to many medications that target ion channels increases the incidence of cleft palate. Cleft palate could be prevented by understanding how ion channels contribute to palatal development. Ion channels regulate the electrical properties of cells. We discovered that the mouse embryonic palate mesenchymal cells are electrically active, like neurons. In neurons, electrical activity regulates transcription cell-autonomously and regulates the secretion of chemical cues. We discovered that electrical activity regulates secretion of bone morphogenetic protein (BMP4) from mouse palate mesenchymal cells. The next important step is to determine how electrical activity affects transcription to control palate development. Loss of a potassium channel called Kcnj2 (<em>Kcnj2</em><sup><em>KO/KO</em></sup>) alters electrical activity in palate mesenchyme cells and causes cleft palate in mice. We compared single cell RNA sequencing datasets from <em>Kcnj2</em><sup><em>KO/KO</em></sup> and wildtype E13.5 mouse anterior palate shelves to define how electrical activity affects gene expression cell autonomously and in surrounding cells. Our data reveal that <em>Kcnj2</em><sup><em>KO/KO</em></sup> alters a network of calcium-induced transcription factors and downstream effectors. These data also reveal that loss of Kcnj2 affects gene expression outside of the cells that express Kcnj2 consistent with disruption of BMP signaling.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 260-274"},"PeriodicalIF":2.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Home for Every Discovery: Article Types at DB","authors":"","doi":"10.1016/j.ydbio.2025.07.015","DOIUrl":"10.1016/j.ydbio.2025.07.015","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Page 97"},"PeriodicalIF":2.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spradling A , Pathak M , Davidian A , Maurya Bhawana , Tiwari A , Yin Q , Fu Y , Mao A
{"title":"Hypothesis: Germline rejuvenation during meiosis underlies animal oogenesis","authors":"Spradling A , Pathak M , Davidian A , Maurya Bhawana , Tiwari A , Yin Q , Fu Y , Mao A","doi":"10.1016/j.ydbio.2025.08.002","DOIUrl":"10.1016/j.ydbio.2025.08.002","url":null,"abstract":"<div><div>Animal oogenesis utilizes features shared among diverse phylogenetic groups, whose functional roles in promoting progeny development have remained unclear. However, germ cells not only produce the next generation, they also maintain long term species integrity by fully restoring acquired damage that deviates from genomic specifications and by controlling parasitic elements that pose a multi-generational threat. Here we discuss how oogenesis “rejuvenates” the germline to sustain the effective immortality needed for species to survive, adapt and evolve. We argue that animal oocytes actively rebuild critical cellular components including organelles during meiosis, usually within an ancient syncytial format, the germline cyst, that enhances renewal mechanisms long inherent to meiosis in single-celled eukaryotes. The Balbiani body accumulates rejuvenated materials and connects them with germ cell inducers relatively early in oogenesis, to ensure genome-quality constituents are inherited by germ cells of the next generation. This strategy explains the existence of germ plasm and why the GV-Bb axis presages the embryo's animal-vegetal axis in diverse species. The advent of a more powerful rejuvenation system may have enabled the evolution of animals.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 65-76"},"PeriodicalIF":2.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meredith L. Becher , Fangyi Coco Zhai , Matthew L. Gilbert , Dariana I. Mota , Leroy A. Griffiths Jr. , Mirsha Pierre , Ashwath R. Athreya , Fiona S. Boyd , Aliya M. Cameron , Meaghan R. Cameron , Stephan E. Desir , Yumeng Han , Jacqueline Kaba , Ondrea J.G. Kerr , Hayden G. Kowalski , Siddhi M. Patel , Dulce G. Pineda , Rhythm Pravasi , Maya D. Ravi , Xinyue Shang , Geoffrey R. Tanner
{"title":"Ketone body supplementation into a standard high-carbohydrate diet reduces fecundity, delays larval development, and may induce autophagy in Drosophila melanogaster","authors":"Meredith L. Becher , Fangyi Coco Zhai , Matthew L. Gilbert , Dariana I. Mota , Leroy A. Griffiths Jr. , Mirsha Pierre , Ashwath R. Athreya , Fiona S. Boyd , Aliya M. Cameron , Meaghan R. Cameron , Stephan E. Desir , Yumeng Han , Jacqueline Kaba , Ondrea J.G. Kerr , Hayden G. Kowalski , Siddhi M. Patel , Dulce G. Pineda , Rhythm Pravasi , Maya D. Ravi , Xinyue Shang , Geoffrey R. Tanner","doi":"10.1016/j.ydbio.2025.07.020","DOIUrl":"10.1016/j.ydbio.2025.07.020","url":null,"abstract":"<div><div>Fasting (typically intermittent; IF), caloric restriction (CR), and the increasingly-popular high-fat, low-carbohydrate ketogenic diet (KD) count among many starvation-mimicking dietary regimens known to exert diverse effects on cellular and whole-organism behavioral, developmental, and physiological parameters. These effects include lowering neuronal excitability, inducing the cellular-component-recycling process of autophagy, altering reproductive outcomes (especially in pathological cases), and extending lifespan. These challenging diet regimens can produce elevated levels of circulating ketone bodies (KBs), which themselves are known to exert numerous potentially-beneficial genetic and signaling effects. We applied KBs as a supplement (KBS) directly into a standard high-carbohydrate (SHC) <em>Drosophila</em> culture-media diet for wild-type flies. We found that KBS reduced female fecundity (measured as egg laying) and significantly delayed larval developmental timelines, possibly via induction of elevated autophagy, of which we detected some evidence in the fat-body organs of third-instar larvae. Our findings suggest that dietary KBS may elevate autophagic processes in the manner of starvation-like dietary regimens. Further, through autophagy-related biochemical and cellular processes, KBS may induce biological responses that may thus help provide health benefits similar to those associated with IF, CR, and the KD itself.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 109-135"},"PeriodicalIF":2.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial: Bridging developmental biology and social justice to reclaim trust in science and society","authors":"Nicole A. Theodosiou, Michael J.F. Barresi","doi":"10.1016/j.ydbio.2025.07.017","DOIUrl":"10.1016/j.ydbio.2025.07.017","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 39-40"},"PeriodicalIF":2.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas S. Diab , Valentyna Kostiuk , Leonid Tyan , Emily Mis , David Zenisek , Mustafa K. Khokha
{"title":"TMBIM4 affects left-right patterning via pluripotency exit during gastrulation","authors":"Nicholas S. Diab , Valentyna Kostiuk , Leonid Tyan , Emily Mis , David Zenisek , Mustafa K. Khokha","doi":"10.1016/j.ydbio.2025.07.018","DOIUrl":"10.1016/j.ydbio.2025.07.018","url":null,"abstract":"<div><div>Congenital heart disease (CHD) is the most prevalent congenital defect, but its underlying genetic and developmental mechanisms remain incompletely understood. Transmembrane BAX inhibitor motif-containing protein 4 (<em>TMBIM4</em>) has emerged as a candidate gene from genomic studies in CHD patients. Patients with deleterious genetic variation in <em>TMBIM4</em> can exhibit cardiac heterotaxy, a type of left-right (LR) patterning defect characterized by abnormal cardiac asymmetry. Using <em>Xenopus tropicalis</em>, we investigated <em>tmbim4's</em> developmental roles and identified its critical function in LR patterning. <em>tmbim4</em> depletion in <em>Xenopus</em> produced cardiac asymmetry defects which could be rescued by human and viral orthologs of the protein, reflecting remarkable evolutionary conservation. We identified gastrulation as a critical window for <em>tmbim4</em> function. <em>tmbim4</em> depletion impairs gastrulation, leading to abnormal pluripotency marker expression and delayed pluripotency exit. TMBIM4's underlying function is as a putative ion channel, and ion channels are emerging as key regulators of LR patterning and cell fate determination. Using sharp electrodes to measure membrane potential (V<sub>m</sub>), <em>tmbim4</em> depletion depolarized affected embryos. The application of choline, which we have previously shown recues depolarization of <em>Xenopus</em> embryos, rescued the gastrulation defects and pluripotency in <em>tmbim4</em> depleted embryos. Interestingly, TMBIM4 has previously been localized to the Golgi, and therefore how it might affect V<sub>m</sub> was unclear. We find evidence that TMBIM4 localizes to the plasma membrane as well as the Golgi suggesting that it may directly act to establish cellular V<sub>m</sub>. Our results establish <em>tmbim4</em> as a plausible CHD gene and offer the first study of <em>tmbim4</em> in a developmental context.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 136-146"},"PeriodicalIF":2.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Germline factors, TDRD and Piwi, colocalize with Vasa on the mitotic apparatus during the embryogenesis of the sea urchin","authors":"Mariana Witmer , Nirali Mehta , Natsuko Emura , Mamiko Yajima","doi":"10.1016/j.ydbio.2025.07.016","DOIUrl":"10.1016/j.ydbio.2025.07.016","url":null,"abstract":"<div><div>Germline factors are thought to function exclusively in the germline, providing the unique characteristics of germ cells. However, recent studies suggest that some of these factors may also be expressed and function outside the germline. One such example includes Vasa, a DEAD-box RNA helicase that appears to control localized translation on the spindle, facilitating efficient protein synthesis during embryogenesis of the sea urchin. However, it remains unclear if other germline factors are also involved in this process. In this study, we investigated the localization dynamics of Vasa's partners in the germline, such as Tudor-domain-containing proteins (TDRDs) and P-element-induced wimpy testis proteins (Piwis). Among TDRDs tested in this study, we found that TDRD7 is enriched on the spindle and forms granules with Vasa during early embryogenesis. Vasa and TDRD7 recruited each other when the expression of either was forced at the membrane, suggesting their interaction with each other. TDRD7 mutants lacking the N-terminal eLOTUS domain or the central intrinsically disordered region exhibited reduced granule formation, which also compromised their recruitment to Vasa. In contrast, PiwiL1/2 and PiwiL3 showed enrichment at the perinuclear region and the spindle, yet were never recruited to Vasa or TDRD7 when either was expressed at the membrane. These results suggest that a group of germline factors is present and may dynamically interact with each other on the spindle, contributing to somatic cell regulation in the sea urchin embryo.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 98-108"},"PeriodicalIF":2.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Ji Bertken , Yeeun Kim , Juan Llamas , Assaf Beck , Aaron Nagiel , Ksenia Gnedeva
{"title":"ShH10 viral vector for safe, efficient, and selective transduction of inner ear supporting cells","authors":"Yun Ji Bertken , Yeeun Kim , Juan Llamas , Assaf Beck , Aaron Nagiel , Ksenia Gnedeva","doi":"10.1016/j.ydbio.2025.07.013","DOIUrl":"10.1016/j.ydbio.2025.07.013","url":null,"abstract":"<div><div>Hearing loss is the most prevalent type of sensory deficit in humans. Recent studies have found adeno-associated viruses (AAVs) targeting hair cells as promising vectors for inner ear gene therapy. However, targeting non-sensory cell types, which are often affected by genetic mutations causing sensorineural hearing loss, remains a challenge. In this study, we characterize the serotype ShH10, an AAV variant we show to have high tropism for supporting cells in the mouse cochlea and utricle. We demonstrate that ShH10 efficiently targets all subtypes of supporting cells along the length of cochlear duct without negatively impacting auditory function. Unlike many other potent AAV vectors tested in the inner ear, ShH10 does not spread to the central nervous system or the contralateral ear, allowing for more targeted therapy. Future studies in disease models and larger animal models will be crucial for validating the clinical potential of this serotype in correcting both genetic and acquired hearing dysfunction.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 289-296"},"PeriodicalIF":2.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiangyang Liu , Jianfeng Wang , Youshi Chen , Hongjun Shi
{"title":"A low-cost, high-throughput pipeline for 3D imaging of embryonic mouse hearts using lightsheet microscopy","authors":"Xiangyang Liu , Jianfeng Wang , Youshi Chen , Hongjun Shi","doi":"10.1016/j.ydbio.2025.07.009","DOIUrl":"10.1016/j.ydbio.2025.07.009","url":null,"abstract":"<div><div>Lightsheet microscopy is a powerful tool for three-dimensional imaging of both live and fixed specimens, spanning small to large scales. However, the time-intensive sample preparation and mounting process often limit its use in high-throughput studies. Given our focus on cardiac development and identifying cardiovascular abnormalities after teratogenic exposure, we have developed an efficient, low-cost, and user-friendly system for specimen fixation, clearing, and mounting. This system enables rapid 3D imaging of a mouse embryonic heart within 1 min using the Zeiss Lightsheet Z.1 microscopy and supports imaging of at least 30 hearts per hour with high resolution. With this system, we obtained high-quality images of embryonic hearts at various stages, visualizing internal structures like the aortic valve and coronary arteries with this system. We further demonstrated its capability for quantitative analysis, including endocardial cushion cell density at E10.5 and volumetric measurements of valve morphology. As an extended application, the system was also applied to postnatal P10 hearts and extra-cardiac organs like kidney and ovary, showing clear structural detail. Additionally, integration of the water-soluble clearing agent, EZ Clear, alongside Cre-loxP-mediated genetic lineage tracing, enabled 3D visualization of cellular contributions to heart development with high resolution. The sample preparation system described here promises broader applications in embryology, anatomy, and pathology research, especially in studies requiring both high throughput and high resolution of 3D imaging.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 26-38"},"PeriodicalIF":2.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}