{"title":"Canonical Wnt pathway modulation is required to correctly execute multiple independent cellular dynamic programs during cranial neural tube closure","authors":"Amber Huffine Bogart, Eric R. Brooks","doi":"10.1016/j.ydbio.2025.04.013","DOIUrl":"10.1016/j.ydbio.2025.04.013","url":null,"abstract":"<div><div>Defects in cranial neural tube closure are among the most common and deleterious human structural birth defects. Correct cranial closure requires the coordination of multiple cell dynamic programs including cell proliferation and cell shape change. Mutations that impact Wnt signaling, including loss of the pathway co-receptor LRP6, lead to defects in cranial neural tube closure, but the cellular dynamics under control of the Wnt pathway during this critical morphogenetic process remain unclear. Here, we use mice mutant for LRP6 to examine the consequences of conditional and global reduction in Wnt signaling and mutants with conditional inactivation of APC to examine the consequences of pathway hyperactivation. Strikingly, we find that regulated Wnt signaling is required for two independent events during cranial neural tube closure. First, global reduction of Wnt leads to a surprising hyperplasia of the cranial neural folds driven by excessive cell proliferation at early pre-elevation stages, with the increased tissue volume creating a mechanical blockade to efficient closure despite normal apical constriction and cell polarization at later stages. Conversely, conditional hyperactivation of the pathway at later elevation stages prevents correct actin organization, blocking apical constriction and neural fold elevation without impacting tissue scaling. Together these data reveal that Wnt signaling levels must be modulated to restrict proliferation at early stages and promote apical constriction at later elevation stages to drive efficient closure of the cranial neural tube.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"523 ","pages":"Pages 115-131"},"PeriodicalIF":2.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873355","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":"Positive-negative Selection: The counterselection breakthrough that conventionalized reverse genetics in the mouse","authors":"Anthea Letsou","doi":"10.1016/j.ydbio.2025.04.004","DOIUrl":"10.1016/j.ydbio.2025.04.004","url":null,"abstract":"<div><div>Mario Capecchi, 2007 Nobel Laureate and Distinguished Professor of Human Genetics at the University of Utah School of Medicine, was instrumental in establishing the mouse as the premier reverse genetic model for studying mammalian development. The Capecchi lab’s innovative research, which combined studies of homologous recombination and mammalian embryo manipulation, changed the trajectory of experimental developmental biology. Crucial in the field was the breakthrough study of Suzanne Mansour, Kirk Thomas, and Mario Capecchi: <em>Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes</em> (Mansour et al., 1988). Published in <em>Nature</em> in 1988, the manuscript which describes positive-negative selection strategies for gene knockout has been cited close to 2500 times. The impact of the work was to revolutionize mouse genetics by enabling the efficient creation of targeted mutations and sophisticated animal models for the analysis of any gene’s function in mammalian development and health. These models have been integral to our understanding of fundamental biological processes and disease mechanisms.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"523 ","pages":"Pages 139-143"},"PeriodicalIF":2.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903904","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":"Genetic assimilation, robustness and plasticity are key processes in the development and evolution of novel traits","authors":"H. Frederik Nijhout","doi":"10.1016/j.ydbio.2025.04.011","DOIUrl":"10.1016/j.ydbio.2025.04.011","url":null,"abstract":"<div><div>This is a commentary on how C.H. Waddington's experiments in the 1950's, first published in 1953 in a provocatively titled paper “Genetic assimilation of an acquired character,” laid the foundation for the field of phenotypic plasticity, and how the ideas he developed eventually led to new ways of understanding phenotypic robustness, plasticity, and how novel traits develop and evolve. The “acquired characters” that Waddington worked with were based on Goldschmidt's ideas of “phenocopies”: new phenotypes that develop after an environmental stress that resemble the phenotypes of known mutations. The idea behind genetic assimilation, first outlined by Waddington in 1942, is that existing developmental pathways can be rearranged and redirected through selection to stabilize the phenocopy phenotype, without requiring new mutations. In the short term, Waddington's work led to the discovery of heat shock proteins and the role of Hsp90 in masking defective proteins and allowing the accumulation of cryptic genetic variation. Subsequent studies revealed a host of stabilizing systems that operate at all levels of biological organization that make phenotypes robust to genetic and environmental variation. Many of these resemble homeostatic mechanisms that don't require a stress shock but operate under normal physiological conditions and allow for the accumulation of large amounts of cryptic genetic variation. This cryptic genetic variation can be revealed by mutations or environmental factors that destabilize a homeostatic mechanism. Selection can then act on the phenotypic variants that are produced. This scenario corresponds to the modern phenotype-first hypothesis for the evolution of novel traits that was foreseen by Waddington as early as 1942.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"523 ","pages":"Pages 132-138"},"PeriodicalIF":2.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879321","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":"Exploring early extraembryonic cells of epiblast origin: Questions on human amniotic ectoderm and extraembryonic mesoderm","authors":"Shota Nakanoh","doi":"10.1016/j.ydbio.2025.04.010","DOIUrl":"10.1016/j.ydbio.2025.04.010","url":null,"abstract":"<div><div>Extraembryonic tissues are essential for proper fetal development and exhibit great diversity across species. Despite its importance, human extraembryonic development has been relatively overlooked. Previously, we established an <em>in vitro</em> model to study human amniogenesis and extraembryonic mesoderm formation. In this article, I develop discussions on four topics inspired by this study: (1) Features of amniotic cell populations described to date. A recently reported early amniotic cell type is examined based on its signature genes to consider how this population should be incorporated into models of primate amniogenesis. (2) Molecular mechanisms underlying the effect of cell density in regulating non-neural ectoderm specification. Fate specification by positional cues in mouse is revisited and possible mechanisms are suggested by drawing insights from human epiblast models. (3) Potential applications of the three-dimensional culture we established. Primate amniotic ectoderm is postulated as a gastrulation-inducing signaling center, and our technique could be used to effectively model its interactions with epiblast. (4) Extraembryonic mesoderm development in human embryos. The obscure origin of primate extraembryonic mesoderm and implications from recent <em>in vitro</em> differentiation models using human pluripotent stem cells are explained. The key concepts explored here will stimulate further studies into both amnion and extraembryonic mesoderm during human and non-human primate development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"524 ","pages":"Pages 80-86"},"PeriodicalIF":2.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936310","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}
Faraz Ahmed Butt , Alessandro De Simone , Stefano Di Talia , Kenneth D. Poss
{"title":"In toto live imaging of Erk signaling dynamics in developing zebrafish hepatocytes","authors":"Faraz Ahmed Butt , Alessandro De Simone , Stefano Di Talia , Kenneth D. Poss","doi":"10.1016/j.ydbio.2025.04.009","DOIUrl":"10.1016/j.ydbio.2025.04.009","url":null,"abstract":"<div><div>Regional and tissue-wide regulation of signaling pathways orchestrates cellular proliferation and differentiation during organ development. In this study, we established an imaging platform for longitudinal analysis of liver development in live developing zebrafish. We generated hepatocyte-specific transgenic lines for kinase translocation reporters of extracellular signal-regulated kinase (Erk) and c-Jun N-terminal kinase (Jnk) signaling, and with these we captured signaling dynamics that govern rapid expansion of hepatocytes toward creation of the functioning liver at single-cell resolution. Our findings reveal Erk signaling fluctuations as the liver develops and introduce methodology for investigating cell-type specific signaling dynamics during organ morphogenesis.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"523 ","pages":"Pages 43-50"},"PeriodicalIF":2.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833179","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":"Unravelling early hematoendothelial development through the chick model: Insights and future perspectives","authors":"Lydia Pouncey, Gi Fay Mok","doi":"10.1016/j.ydbio.2025.04.008","DOIUrl":"10.1016/j.ydbio.2025.04.008","url":null,"abstract":"<div><div>The chicken embryo has been an important model in advancing our understanding of early hematoendothelial development, particularly in the formation of hematopoietic stem cells (HSCs) and the endothelial-to-hematopoietic transition (EHT). The accessibility and ease of manipulation of chicken embryos have made them an invaluable tool for researching development of blood and endothelial cells. Early research using this model provided pivotal insights, demonstrating that intra-embryonic regions, such as the dorsal aorta (DA), are primary sources of HSCs, rather than the yolk sac (YS), as previously believed. The identification of intra-aortic hematopoietic clusters (IAHCs) and the process of EHT in the chicken embryo laid the foundation for similar discoveries in other vertebrate species, including mice and zebrafish. Recent advances in genetic tools, such as transgenic chickens expressing fluorescent proteins, have further enhanced the precision of cell lineage tracing and real-time imaging of dynamic cellular processes. This review highlights both historical contributions and contemporary advancements facilitated by the chicken model, underscoring its continued relevance in developmental biology. By examining key findings and methodological innovations, we aim to demonstrate the importance of the chicken embryo as a model system for understanding hematoendothelial development and its potential for informing therapeutic applications in regenerative medicine and blood disorders. Finally, we will underscore potential applications of the chicken model for comparative and omics-level studies in conjunction with other model systems and what future directions lie ahead.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"523 ","pages":"Pages 20-31"},"PeriodicalIF":2.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828888","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}
Fanning Xia, Ana Santacruz , Di Wu, Sylvain Bertho, Elizabeth Fritz, Pedro Morales-Sosa, Sean McKinney, Stephanie H. Nowotarski, Nicolas Rohner
{"title":"Reproductive adaptation of Astyanax mexicanus under nutrient limitation","authors":"Fanning Xia, Ana Santacruz , Di Wu, Sylvain Bertho, Elizabeth Fritz, Pedro Morales-Sosa, Sean McKinney, Stephanie H. Nowotarski, Nicolas Rohner","doi":"10.1016/j.ydbio.2025.04.006","DOIUrl":"10.1016/j.ydbio.2025.04.006","url":null,"abstract":"<div><div>Reproduction is a fundamental biological process for the survival and continuity of species. Examining changes in reproductive strategies offers valuable insights into how animals have adapted their life histories to different environments. Since reproduction is one of the most energy-intensive processes in female animals, nutrient scarcity is expected to interfere with the ability to invest in gametes. Lately, a new model to study adaptation to nutrient limitation has emerged; the Mexican tetra <em>Astyanax mexicanus</em>. This fish species exists as two different morphs, a surface river morph and a cave-dwelling morph. The cave-dwelling morph has adapted to the dark, lower biodiversity, and nutrient-limited cave environment and consequently evolved an impressive starvation resistance. However, how reproductive strategies have adapted to nutrient limitations in this species remains poorly understood. Here, we compared breeding activities and maternal contributions between laboratory-raised surface fish and cavefish. We found that cavefish produce different clutch sizes of eggs with larger yolk compared to surface fish, indicating a greater maternal nutrient deposition in cavefish embryos. To systematically characterize yolk compositions, we used untargeted proteomics and lipidomics approaches to analyze protein and lipid profiles in 2-cell stage embryos and found an increased proportion of sphingolipids in cavefish compared to surface fish. Additionally, we generated transcriptomic profiles of surface fish and cavefish ovaries using a combination of single cell and bulk RNA sequencing to examine differences in maternal contribution. We found that genes essential for hormone regulation were upregulated in cavefish follicular somatic cells compared to surface fish. To evaluate whether these differences contribute to their reproductive abilities under natural-occurring stress, we induced breeding in starved female fish. Remarkably, cavefish maintained their ability to breed under starvation, whereas surface fish largely lost this ability. We identified <em>insulin-like growth factor 1a receptor</em> (<em>igf1ra</em>) as a potential candidate gene mediating the downregulation of ovarian development genes, potentially contributing to the starvation-resistant fertility of cavefish. Taken together, we investigated the female reproductive strategies in <em>Astyanax mexicanus</em>, which will provide fundamental insights into the adaptations of animals to environments with extreme nutrient deficit.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"523 ","pages":"Pages 82-98"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859934","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}
Shinuo Weng , Caitlin C. Devitt , Bill M. Nyaoga , José Alvarado , John B. Wallingford
{"title":"PCP-dependent polarized mechanics in the cortex of individual cells during convergent extension","authors":"Shinuo Weng , Caitlin C. Devitt , Bill M. Nyaoga , José Alvarado , John B. Wallingford","doi":"10.1016/j.ydbio.2025.04.007","DOIUrl":"10.1016/j.ydbio.2025.04.007","url":null,"abstract":"<div><div>Convergent extension (CE) is a key process for tissue elongation during vertebrate development and is driven by polarized cell behaviors. Here, we used a novel image-based technique to investigate the mechanical properties of individual cells undergoing CE. Our results suggest a PCP- and Septin-dependent mechanical gradient, where cortical tension is higher at the anterior face of the cells compared with their posterior face. Disruption of PCP protein Vangl2 or its downstream effector Septin7 eliminates this mechanical polarity. These findings demonstrate a link between actin organization, PCP signaling, and mechanical polarization, providing new avenues into the mechanochemical regulation of cellular behaviors during CE.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"523 ","pages":"Pages 59-67"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839508","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":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S0012-1606(25)00097-1","DOIUrl":"10.1016/S0012-1606(25)00097-1","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"522 ","pages":"Page OBC"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815009","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}
Cameron Batho-Samblas , Jonathan Smith , Lois Keavey , Noah Clancy , Lynn McTeir , Megan G. Davey
{"title":"Characterisation of the avascular mesenchyme during digit outgrowth","authors":"Cameron Batho-Samblas , Jonathan Smith , Lois Keavey , Noah Clancy , Lynn McTeir , Megan G. Davey","doi":"10.1016/j.ydbio.2025.04.005","DOIUrl":"10.1016/j.ydbio.2025.04.005","url":null,"abstract":"<div><div>The avascular mesenchyme at the tip of the developing digit contributes to digit outgrowth and patterning, however, it has been poorly characterised. Using newly developed fate mapping approaches, tissue manipulation and single-cell mRNA sequencing data, we explore the transcriptional nature and developmental potential of this tissue. We find that the avascular mesenchyme is essential to normal segmental patterning of the digit and has a distinct transcriptional identity. In addition, we uncover an unexpected relationship between the unspecified tissue of the avascular mesenchyme and the committed phalanx forming region, which controls patterning, but not outgrowth of the digit. This multifaceted approach provides insights into the mechanics and genetic pathways that regulate digit outgrowth and patterning.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"523 ","pages":"Pages 99-110"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863603","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}