The International journal of developmental biology最新文献

Intrauterine growth restriction (IUGR) is increasingly recognized as a significant risk factor for metabolic disorders in adulthood. Employing a multi-faceted approach encompassing histopathological, immunohistochemical, biochemical, Western-blotting, and metabolomics analyses, this study aimed to elucidate potential metabolite markers of IUGR, and catch-up growth-related metabolic disturbances and the underlying metabolic pathways implicated in IUGR pathogenesis. This study cohort comprised 54 male siblings from 20 Sprague-Dawley female young rats. On the 19th day of gestation, half of the pregnant rats underwent bilateral uterine artery ligation, while the remaining half underwent a simulated surgical intervention involving solely peritoneal incisions. Blood and liver samples were collected from the pups after attaining catch-up growth at the postnatal weeks 2, 4, and 8. IUGR rats exhibited a spectrum of changes including histological abnormalities, altered apoptosis rates, oxidative stress markers, and mitochondrial energy metabolism. Metabolomic analysis revealed dysregulation in multiple metabolic pathways encompassing galactose, propanoate, glycerolipid, cysteine, methionine, and tyrosine metabolism, among others. Notably, disturbances were observed in butanoate, glutathione metabolism, valine, leucine, and isoleucine biosynthesis and degradation, citrate cycle, aminoacyl-tRNA biosynthesis, as well as glycolysis/gluconeogenesis. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, heart failure, cancer, mental retardation, kidney and liver diseases, and cataracts. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies aimed at mitigating the risk of metabolic diseases in individuals with a history of IUGR.

This study investigated the role of cyclooxygenase-2 (COX2) in angiogenesis during zebrafish embryogenesis by inhibiting COX2 activity with etoricoxib. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis confirmed the successful penetration of etoricoxib into zebrafish embryos, leading to selective inhibition of COX2 without affecting COX1 activity. COX2 inhibition caused a significant reduction in prostaglandin E₂ levels throughout development. Phenotypically, treated embryos exhibited pericardial edema, bradycardia, and defective vascular development, including delays in intersegmental vessel (ISV) sprouting, incomplete dorsal longitudinal anastomotic vessel (DLAV) formation by 48 hpf, and impaired vascular networks by 72 hpf. Confocal imaging and AngioTool analysis revealed reduced vessel length, area and increased lacunarity. Molecular analysis showed significant downregulation of vascular endothelial growth factor A (vegfa), kdr, pi3k and akt transcripts, as well as reduced VEGFA, EP4 and Akt protein levels, disrupting VEGFA-PI3K-Akt signaling. Additionally, reduced expression of ephrinb and prox1 affected arterial and venous identity formation. These results demonstrate that COX2 is essential for proper angiogenesis during zebrafish development, and its inhibition leads to significant vascular defects, underscoring COX2's crucial role in regulating VEGFA-mediated angiogenesis.

The axolotl, a legendary creature with the potential to regenerate complex body parts, is positioned as a powerful model organism due to its extraordinary regenerative capabilities. Axolotl can undergo successful regeneration of multiple structures, providing us with the opportunity to understand the factors that exhibit altered activity between regenerative and non-regenerative animals. This comprehensive review will explore the mysteries of axolotl regeneration, from the initial cellular triggers to the intricate signaling cascades that guide this complex process. We will delve deeply into the multifaceted interplay of genes and factors, highlighting the key role of signaling pathways and the influence of epigenetic modifications (such as DNA methylation, histone modification, and miRNA regulation) during regeneration. Furthermore, we will discuss how axolotls defy the odds by showing remarkable resistance to cancer, offering insights into potential therapeutic strategies. However, that is not the end; we will also highlight how age might affect the regenerative power of this creature. We hope this review will help navigate the awe-inspiring realm of axolotl regeneration, advance our understanding of regenerative biology, and chart pathways for future investigations aimed at uncovering new therapeutic approaches.

The neural crest (NC) is an embryonic cell population with high migratory capacity. It contributes to forming several organs and tissues, such as the craniofacial skeleton and the peripheral nervous system of vertebrates. Both pre-migratory and post-migratory NC cells are plastic, adopting multiple differentiation paths by responding to different inductive environmental signals. Cephalic neural crest cells (CNCCs) give rise to most of the cartilage and bone tissues in the head. On the other hand, the mesenchymal potential of trunk neural crest cells (TNCCs) is sparsely detected in some animal groups. The mesenchymal potential of TNCCs can be unveiled through specific environmental conditions of NC cultures. In this study, we present evidence that FGF8 treatment can foster increased chondrogenic differentiation of TNCCs, particularly during treatment at the migratory stage. Additionally, we conducted a transcriptomic analysis of TNCCs in the post-migratory stage, noting that exogenous FGF8 signaling can sustain multipotent status and, possibly, at the same time, a pro-cartilage regulatory gene network. Our results provide a more comprehensive understanding of the mechanisms underlying chondrogenic differentiation from TNCCs.

Aggregates of two mouse embryos produce viable offspring of normal size, indicating that there are mechanisms in the embryo that can downregulate their size to the size of the corresponding normal (single) embryos. Very little is known about the mechanisms controlling compensation for increased preimplantation size. Also, it is still elusive when exactly during development chimeric embryos regulate their size. Here, we determined the exact period of size regulation in chimeras. Using a chimeric embryo produced by aggregating two 8-cell stage embryos, we revealed that size regulation initiates shortly after implantation (E5.5) and ends with the start of gastrulation (E7.5). Importantly, processes that regulate cell number in chimeric embryos do not disturb morphogenesis, so that the formation of the proamniotic cavity occurs in parallel with size regulation.

The presence of horns in domestic ruminants, such as cattle, sheep and goats, has financial and welfare implications. The genetic interactions that lead to horn development are not known. Hornless, or polled, cattle occur naturally. The known causative DNA variants (Celtic, Friesian, Mongolian and Guarani) are in intergenic regions on bovine chromosome 1, but their functions are not known. It is thought that horns may be derived from cranial neural crest stem cells and the POLLED variants disrupt the migration or proliferation of these cells. Relaxin family peptide receptor 2 (RXFP2) is more highly expressed in developing horns in cattle compared to nearby skin and has been shown to play a role in horn development in sheep. However, the role of RXFP2 in horn formation is not understood. Histological analyses of cranial tissues from homozygous horned and polled cattle fetuses at day 58 of development was carried out to determine the differences in the structure of the horn bud region. Condensed cells were only observed in the horn bud mesenchyme of horned fetuses and could be the progenitor horn cells. The distribution of neural crest markers (SOX10 and NGFR) and RXFP2 between horned and polled tissues by immunohistochemistry was also analysed. However, SOX10 and NGFR were not detected in the condensed cells, and therefore, these cells are either not derived from the neural crest, or have differentiated and no longer express neural crest markers. SOX10 and NGFR were detected in the peripheral nerves, while RXFP2 was detected in peripheral nerves and in the horn bud epidermis. Previous research has shown that RXFP2 variants are associated with horn phenotypes in cattle an sheep. Therefore, the RXFP2 variants may affect the development of the epidermis or peripheral nerves in the horn bud.

The digestive tract is a series of organs with specific functions and specialized anatomy. Each organ is organized similarly with concentric layers of epithelial, connective, smooth muscle, and neural tissues. Interstitial cells of Cajal (ICC) are distributed in smooth muscle layers and contribute to the organization of repetitive and rhythmic smooth muscle contractions. Understanding ICC development is critical to understanding gastrointestinal motility patterns. Experiments determining ICC origin and development in mice, chicken, and humans are described, as well as what is known in the zebrafish. At least six types of ICC in the digestive tract have been described and ICC heterogeneity in adult tissues is reviewed. Factors required for ICC development and for maintenance of ICC subclasses are described. This review is suitable for those new to ICC development and physiology, especially those focused on using zebrafish and other model systems.

The tRNA-histidine guanylyltransferase 1-like (THG1L), also known as induced in high glucose-1 (IHG-1), encodes for an essential mitochondria-associated protein highly conserved throughout evolution, that catalyses the 3'-5' addition of a guanine to the 5'-end of tRNA-histidine (tRNA^His). Previous data indicated that THG1L plays a crucial role in the regulation of mitochondrial biogenesis and dynamics, in ATP production, and is critically involved in the modulation of apoptosis, cell-cycle progression and survival, as well as in cellular stress responses and redox homeostasis. Dysregulations of THG1L expression play a central role in various pathologies, including nephropathies, and neurodevelopmental disorders often characterized by developmental delay and cerebellar ataxia. Despite the essential role of THG1L, little is known about its expression during vertebrate development. Herein, we examined the detailed spatio-temporal expression of this gene in the developing Xenopus laevis. Our results show that thg1l is maternally inherited and its temporal expression suggests a role during the earliest stages of embryogenesis. Spatially, thg1l mRNA localizes in the ectoderm and marginal zone mesoderm during early stages of development. Then, at tadpole stages, thg1l transcripts mostly localise in neural crests and their derivatives, somites, developing kidney and central nervous system, therefore largely coinciding with territories displaying intense energy metabolism during organogenesis in Xenopus.

Invertebrate and vertebrate species have many unusual cellular structures, such as long- or short-lived cell-in-cell structures and coenocytes. Coenocytes (often incorrectly described as syncytia) are multinuclear cells derived, unlike syncytia, not from the fusion of multiple cells but from multiple nuclear divisions without cytokinesis. An example of a somatic coenocyte is the coenocytic blastoderm in Drosophila. An astonishing property of coenocytes is the ability to differentiate the nuclei sharing a common cytoplasm into different subpopulations with different fate trajectories. An example of a germline coenocyte is the oogenic precursor of appendicularian tunicates, which shares many features with the somatic coenocyte of Drosophila. The germline coenocyte (coenocyst) is quite an unexpected structure because in most animals, including Drosophila, Xenopus, and mice, oogenesis proceeds within a group (cyst, nest) of sibling cells (cystocytes) connected by the intercellular bridges (ring canals, RCs) derived from multiple divisions with incomplete cytokinesis of a progenitor cell called the cystoblast. Here, I discuss the differences and similarities between cystocyte-based and coenocyst-based oogenesis, and the resemblance of coenocystic oogenesis to coenocytic somatic blastoderm in Drosophila. I also describe cell-in-cell structures that although not mechanistically, cytologically, or molecularly connected to somatic or germline coenocytes, are both unorthodox and intriguing cytological phenomena rarely covered by scientific literature.

During embryonic development, the vertebrate embryonic epiblast is divided into two parts including neural and superficial ectoderm. The neural plate border (NPB) is a narrow transitional area which locates between these parts and contains multipotent progenitor cells. Despite its small size, the cellular heterogeneity in this region produces specific differentiated cells. Signaling pathways, transcription factors, and the expression/repression of certain genes are directly involved in these differentiation processes. Different factors such as the Wnt signaling cascade, fibroblast growth factor (FGF), bone morphogenetic protein (BMP) signaling, and Notch, which are involved in various stages of the growth, proliferation, and differentiation of embryonic cells, are also involved in the determination and differentiation of neural plate border stem cells. Therefore, it is essential to consider the interactions and temporospatial coordination related to cells, tissues, and adjacent structures. This review examines our present knowledge of the formation of the neural plate border and emphasizes the requirement for interaction between different signaling pathways, including the BMP and Wnt cascades, the expression of its special target genes and their regulations, and the precise tissue crosstalk which defines the neural crest fate in the ectoderm at the early human embryonic stages.