Development Growth & Differentiation最新文献

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.

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.

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.

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.

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, Drosophila melanogaster 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 D. melanogaster . 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 D. melanogaster 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’.]

The in situ hybridization chain reaction (HCR) method involves designing multiple target sequences and a pair of split probes for each target. One split probe contains the complementary sequence for half of the target along with part of the initiation sequence. The other split probe contains the complementary sequence for the remaining half of the target sequence and the rest of the initiation sequence. The complete initiation sequence composed of both probes is capable of initiating a chain reaction of hairpin DNAs. This theoretical mechanism minimizes the background signal caused by a single probe; however, very low background signals have been observed in experiments. While these weak signals are not a significant problem in many cases, they can interfere with experiments if the expression of the target gene is very low, making the background signal noticeable. Reducing such background signals would benefit many scientists working with diverse species and sample types. To address this issue, we hypothesized that a single probe could bind and open the hairpin DNA through partial complementary sequences, acting as a bridge between hairpin DNA and samples through nonspecific binding. Our findings show that the addition of random oligonucleotides during the pre-hybridization and hybridization steps reduced background signals by approximately 3–90 times. This simple and easy modification of the in situ HCR technique improves the signal-to-noise ratio and facilitates the detection of mRNAs with very low expression levels.