{"title":"Expression of hox Genes and Genes Related to Limb Development During the Homeotic Transformation of Tails Into Limbs Induced by Vitamin A in the Anuran Rana ornativentris.","authors":"Sho Morioka, Yoshio Yaoita, Keisuke Nakajima, Nobuaki Furuno, Ichiro Tazawa","doi":"10.1111/dgd.70027","DOIUrl":"https://doi.org/10.1111/dgd.70027","url":null,"abstract":"<p><p>Anuran tadpoles regenerate their tails after amputation. However, when vitamin A is administered, some anuran species such as Rana ornativentris occasionally form ectopic limbs instead of tail. Few analyses of this phenomenon at the molecular level exist. To investigate the molecular mechanisms underlying ectopic limb development, we quantified the expression of genes related to normal limb positioning and development. We observed the downregulation of a posterior hox gene prior to the appearance of ectopic limb buds in the regenerating tail. This hox expression change also preceded the upregulation of pitx1, which is expressed in the earliest hind limb bud. These results suggest that Hox genes are involved in ectopic limb induction upstream of hind limb genes.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fate and Specification of the Ventral Endoderm in and Outside the Foregut of the Avian Embryo at 9-12 Somite Stage.","authors":"Susumu Matsushita, Koko Urase","doi":"10.1111/dgd.70025","DOIUrl":"https://doi.org/10.1111/dgd.70025","url":null,"abstract":"<p><p>The fate and specification of the endoderm lining the ventral foregut and outside the foregut cranial to the anterior intestinal portal of the 9-12 somite stage avian embryo were analyzed to determine whether this endoderm was specified according to its fate. The ventral foregut endoderm contributed to the ventral endoderm of the gut from the pharynx to the duodenum, and to the thyroid, respiratory organ, and liver. Pre-pharyngeal cells were distributed throughout the ventral foregut, with pre-thyroid cells lying medially in the anterior to middle part and pre-pharyngeal pouch cells lying laterally. Progenitors of posterior organs from the esophagus to the liver were found in the posteriormost quarter, with those of more posterior organs located in more posterior and medial locations. In the endoderm outside the foregut, progenitors of the liver, ventral jejunum, and extraembryonic endoderm were found, with those of more posterior organs taking more anterior locations. When cultured with somatic mesoderm, most parts of the ventral foregut endoderm showed pharynx/esophagus-like differentiation, whereas the middle part developed thyroid-like follicles. The posteriormost part exhibited stomach-like differentiation, as well as intestinal and pancreatic differentiation, which also appeared from the endoderm outside the foregut. It showed no or a rare appearance of a hepatic cord-like structure or albumin, respectively, but often developed bile duct-like Hex-expressing epithelia. However, the expression of Nkx2.1 but not of Hex, which is characteristic of the pulmonary epithelium, was not observed. These endoderms are likely to be specified in almost complete accordance with their fate, except for the respiratory organ.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roles of Extracellular Superoxide Dismutase in Regulating Cell Migration and Vesicle Trafficking in Dictyostelium and Mammalian Cells.","authors":"Lou W Kim","doi":"10.1111/dgd.70026","DOIUrl":"https://doi.org/10.1111/dgd.70026","url":null,"abstract":"<p><p>Superoxide dismutases (SODs) are key regulators of reactive oxygen species (ROS) and redox balance. Although intracellular SODs have been extensively studied, growing attention has been directed toward understanding the roles of extracellular SODs in both Dictyostelium and mammalian systems. In Dictyostelium discoideum, SodC is a glycosylphosphatidylinositol (GPI)-anchored enzyme that modulates extracellular superoxide to regulate Ras, PI3K signaling, and cytoskeletal remodeling during directional cell migration. Loss of SodC leads to persistent Ras activation, impaired migration, and defective vesicle trafficking, including contractile vacuole (CV) morphogenesis and function. The mammalian EC-SOD (SOD3) localizes not only on the extracellular heparin-binding sites but also within vesicular compartments such as phagosomes, secretory vesicles, and exosomes. EC-SOD limits inflammation, preserves the extracellular matrix, modulates immune and cancer cell migration, and modulates Ras-Erk and PI3K-PKB signaling pathways. Despite evolutionary divergences, both SodC in Dictyostelium and EC-SOD in humans serve to modulate extracellular oxidative cues and maintain cellular function. The conserved and multifaceted roles of extracellular SODs in redox regulation, signaling, vesicle trafficking, and cell migration offer insights relevant to both fundamental biology and disease.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrating Tissue and Cytoplasmic Rigidity Transitions During Morphogenesis","authors":"Sameer Thukral, Bipasha Dey, Yu-Chiun Wang","doi":"10.1111/dgd.70024","DOIUrl":"10.1111/dgd.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>Multicellular organisms generate organizational complexity through morphogenesis, in which mechanical forces orchestrate the movements and deformations of cells and tissues, while chemical signals regulate the molecular events that generate and coordinate these forces. One common denominator that is critical both for mechanics and biochemistry is material property. Material properties define how materials deform or rearrange under applied forces, and how rapidly molecules interact or spread in space and time. Notably, at the two length scales that are highly relevant to multicellular morphogenesis—tissue and cytoplasmic—material properties undergo rigidity transitions. For example, tissue structures transition between fluid-like and solid-like states, while cytoplasm undergoes changes in the degrees of crowdedness and diffusivity. These transitions in space and time, as well as their underlying mechanisms, have emerged as a crucial area of research for the understanding of morphogenesis. However, tissue-scale and cytoplasmic transitions have thus far been studied primarily in separate settings designed specifically for each length scale, even though tissue properties typically arise from cellular and cytoplasmic processes—such as cell–cell adhesion, cell motility, membrane/cortical tension, and intracellular signaling, while cells themselves operate within tissues, responding to mechanical and chemical signals that spread across them. Here we review the mechanisms controlling rigidity transitions at both scales and propose an integrated, multi-scale perspective, in which we explore plausible feedback mechanisms that can link the two scales. By bridging this conceptual gap, we aim to forecast new biological mechanisms that control morphogenesis beyond the physical principles governing rigidity transitions in inert systems.</p>\u0000 </div>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"67 7","pages":"378-394"},"PeriodicalIF":1.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Super-Enhancer-Mediated DLX5 Activation Defines Regulatory Mechanisms in Human Embryonic Stem Cell-Derived Osteoblasts","authors":"Shinse Fujita, Shoichiro Tani, Hiroyuki Okada, Taku Saito, Sakae Tanaka, Shinsuke Ohba, Ung-il Chung, Hironori Hojo","doi":"10.1111/dgd.70023","DOIUrl":"10.1111/dgd.70023","url":null,"abstract":"<p>Osteoblast differentiation is essential for skeletal development and homeostasis. Although bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are commonly used to study osteoblast differentiation in the context of bone homeostasis, their relevance to osteoblast differentiation during human skeletal development remains unclear. To understand the regulatory mechanisms underlying osteoblast differentiation in a human developmental context, we performed Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) and RNA-seq analyses on osteoblasts isolated from an in vivo implantation system using induced sclerotome derived from Col2.3-GFP reporter human embryonic stem cells (hESCs). The resulting datasets revealed skeletal development-associated chromatin accessibility and transcriptional profiles. Comparative analysis with BM-MSC-derived osteoblasts revealed that hESC-derived osteoblasts were enriched for regulatory gene sets associated with ossification. Notably, we identified a super-enhancer associated with <i>DLX5</i>, a known osteoblast regulator, consisting of multiple cooperative enhancer elements to drive transcription. Taken together, this study provides a valuable resource for examining cis–trans regulatory mechanisms in human skeletal development and highlights <i>DLX5</i> as a key transcriptional regulator controlled by an osteoblast super-enhancer.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"67 7","pages":"406-416"},"PeriodicalIF":1.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histone Demethylation Activity of UTX Contributes to the Regulation of Steroid Biosynthesis Genes in Embryonic Gonads but Is Dispensable for Gonadal Sex Determination","authors":"Mio Kojima, Mayu Fujita, Tokuko Iwamori, Ryosuke Honda, Kyoichiro Shima, Yushin Araki, Takumu Tsuhako, Naoki Iwamori","doi":"10.1111/dgd.70022","DOIUrl":"10.1111/dgd.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>Mammalian sex is determined by the presence or absence of a Y chromosome. The sex-specific features of each cell and tissue in the body then develop in response to the sex hormones secreted by the differentiated reproductive tissues. Both the X and Y chromosomes encode histone demethylases. However, the involvement of these histone demethylases in the development of sex differences in each cell is still unknown. One X-linked demethylase, UTX, is also predicted to have both demethylase-dependent and -independent functions. In this study, we generated UTX mutant mice in which the histone demethylase activity of UTX was decreased to disrupt only the demethylase-dependent but not the demethylase-independent function of UTX. Although UTX mutant mice are viable, fertile, and never displayed sex reversal, the expression levels of sex differentiation genes were affected. Transcriptomic analyses revealed that there was a female expression pattern bias in UTX mutant males. Moreover, the steroid biosynthesis pathway was highly affected by the UTX mutation in males, with a significant decrease in the expression of the majority of steroidogenic genes. These results suggest that the demethylation activity of UTX could contribute to the development of sex differences by the regulation of steroid biosynthesis. Further analyses using the UTX mutant mice generated in this study will provide useful information to understand how sex differences develop.</p>\u0000 </div>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"67 7","pages":"417-426"},"PeriodicalIF":1.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell Tracing by a Multicolor Reporter Transgenic Iberian Ribbed Newt Pleurodeles waltl","authors":"Shinichi Hayashi, Ryohei Seki-Omura, Yuki Sato, Souichi Oe, Taro Koike, Yousuke Nakano, Hikaru Iwashita, Yukie Hirahara, Masaaki Kitada","doi":"10.1111/dgd.70021","DOIUrl":"10.1111/dgd.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>Living organisms exhibit varying regenerative abilities depending on the species. Among them, urodele amphibians have been widely used in regeneration biology due to their remarkable regenerative capacity. Iberian ribbed newts, in particular, have been established as a prominent model for regeneration research, offering advantages such as a large number of eggs spawned, a short period of sexual maturation, and the development of genetic manipulation techniques. Cell tracing is an essential method for deciphering cellular processes during organ regeneration. The multicolor reporter Brainbow, which stochastically manifests multiple fluorescent proteins based on the Cre/lox recombination system, has been utilized for clonal analysis in regenerative animal models. In this study, we aimed to utilize this valuable multicolor reporter in Iberian ribbed newts, which are gaining increasing importance as a regenerative animal model. We generated transgenic Iberian ribbed newts carrying the Brainbow3.0 reporter cassette under the control of the CAG (cytomegalovirus early enhancer/chicken beta-actin promoter/rabbit beta-globin splice acceptor) promoter. Cre recombinase induction via electroporation led to recombinant reporter expression in the brain, spinal cord, and muscle. Recombinant reporter-expressing cells could be traced in regenerating tail muscle, midbrain, and spinal cord. Additionally, we applied laser ablation to reporter-positive epithelial cells of Brainbow3.0 newts, enabling clonal analyses at the cellular level. We expect that this long-lasting multicolor reporter will prove versatile for a broad range of research fields.</p>\u0000 </div>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"67 7","pages":"395-405"},"PeriodicalIF":1.0,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Foxg1 and Retinoic Acid Signaling Regulate Zonal Patterning in the Developing Olfactory Epithelium","authors":"Anzu Kuriyama, Carina Hanashima","doi":"10.1111/dgd.70020","DOIUrl":"10.1111/dgd.70020","url":null,"abstract":"<p>Odor information processing begins in the olfactory epithelium (OE), which in mice is spatially divided into two zones: the dorsomedial zone (D-zone), responsible for innate aversive behaviors, and the ventrolateral zone (V-zone), associated with learning-dependent behaviors. This zonal organization provides the structural framework for olfactory circuit function. However, the mechanisms driving OE zonal specification remain unclear. To investigate the initial segregation of the OE zones, we examined the role of Foxg1, a forkhead transcription factor expressed in the V-zone throughout life. Conditional deletion of <i>Foxg1</i> in Sox2-expressing OE stem cells, coupled with lineage tracing, revealed ectopic localization of <i>Foxg1</i>-lineage cells in the D-zone, without altering their regional molecular profile. These results demonstrate that Foxg1 is essential for zonal segregation but is dispensable for zone-specific molecular identity. We further revealed retinoic acid (RA) as an upstream morphogen regulating D-zone-specific gene expression. RA signaling is tightly confined to the D-zone, ensuring OE regional identity. These findings suggest that the establishment of D- and V-zones is driven by interactions between morphogenic signal and transcriptional program involving Foxg1, providing a molecular basis for understanding the formation of innate and learned olfactory circuits.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"67 6","pages":"314-330"},"PeriodicalIF":1.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the Molecular Pathogenesis of MCPH: Insights From Drosophila Model System","authors":"Degisew Yinur Mengistu","doi":"10.1111/dgd.70019","DOIUrl":"10.1111/dgd.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Primary microcephaly (MCPH) is a rare genetic neurodevelopmental disorder caused by homologous recessive mutations of the MCPH genes. It manifests as a significant reduction in brain volume and intellectual disability at birth. More than 28 genes with several pathogeneses have been identified so far. These genes have a strong effect on DNA damage repair and apoptosis, neuronal proliferation, neuronal differentiation, and neuronal migration. These pathogenesis pathways result in aberrant cell division and cell maturation, as well as an imbalance of the type of neural cells, and eventually a reduction of brain volume. Hence, researching in a multidisciplinary approach promotes research into the different etiologies of MCPH genes and offers a positive outcome for patients. However, investigating the etiology pathways has been given less focus, and limited studies and model systems have been carried out for this complex disease. Research using simple model organisms to study these pathogenic genes is beneficial. Recently, \u0000 <i>Drosophila melanogaster</i>\u0000 has been used as a powerful and promising model organism for efficient in vivo experiments and for deciphering complex multicellular activities to unravel the function of the MCPH genes. Interestingly, about 80% of the genes that cause genetic diseases in humans have functional counterparts in \u0000 <i>D. melanogaster</i>\u0000 . Additionally, genetic similarity, simple genetics, rapid reproduction, high-throughput screening, and ease of generating transgenics make it unique. These features have prompted researchers to widely use it in research, contributing significantly to our understanding of human diseases such as cancer, Alzheimer's disease, Parkinson's disease, MCPH, and muscular dystrophy. In this review, I focus on the various pathways of MCPH genes pathogenesis and the advantage of leveraging the \u0000 <i>D. melanogaster</i>\u0000 model to dissect the etiology of MCPH genes. [Correction added on 9 August 2025, after first online publication: In the Abstract section, last sentence, pronoun ‘we’ has been changed to ‘I’.]</p>\u0000 </div>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"67 6","pages":"354-374"},"PeriodicalIF":1.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficient and Easy-Dyeing Method of Whole-Mount Skeletal Staining","authors":"Seiji Saito, Nobuyuki Hibino, Momoko Kyu-shin, Saya Miura, Takayuki Suzuki","doi":"10.1111/dgd.70017","DOIUrl":"10.1111/dgd.70017","url":null,"abstract":"<p>One of the most widely used methods for phenotypic analysis in developmental biology is whole-mount skeletal staining of mice. In this method, cartilage and bone are stained using two types of reagents, Alcian blue and Alizarin red, to observe the skeletal pattern of the whole body. Several experimental methods have been reported for whole-mount skeletal staining. Creating skeletal specimens that are clearly visible is possible using these methods. However, staining all high-quality samples to observe a large number of skeletal specimens takes considerable time and effort. Therefore, in this paper, we review and modify the conventional protocol and describe an efficient and simple experimental method that we use to observe the morphology of the vertebrae and digit patterns at the tips of the hands and feet, in a manner similar to other methods. We also explain the details of the experimental method for fabricating skeletal specimens using a conventional protocol and a unique potassium hydroxide (KOH) processing method. Herein, we present a simple method for the efficient fabrication of several skeletal specimens.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"67 6","pages":"344-353"},"PeriodicalIF":1.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}