The International journal of developmental biology最新文献

Recent studies suggest that tail regeneration in lizards begins with a tumor-like stage usually termed regenerative blastema. Oncogenes and tumor suppressors are activated in blastema cells, resulting in a balanced cell proliferation that does not turn the blastema into a tumor. This outgrowth elongates forming new tissues and tail. We previously showed that physiological extracts from regenerating lizard tissues inhibit the growth of cancer cells in vitro within 2-4 days of administration, demonstrating that the growing lizard blastema contains regulatory molecules which can also influence human cancer cells. The molecules responsible for this inhibition were not identified in that initial study. In the present experimental study, after specific extractions of RNAs and/or proteins from the regenerating tail of lizard, we have confirmed the inhibition of breast cancer cell vitality in vitro within 2-3 days from their addition to the culture medium. Proteolysis or heat denaturation of proteins abolished the inhibitory effect. RNA delivered to breast cancer cells in vitro through lipid vesicles (liposomes) showed the highest inhibition of cancer cells vitality. Cell degeneration, detected by microscopy, revealed that RNA is more effective than proteins extracted from regenerating tissues. The present observations further suggest that RNAs coding for known tumor suppressor proteins, and non-coding RNAs that are highly expressed in the regenerating tail, may be key inhibitors (tumor suppressors) of blastema and cancer cell proliferation. The evolution of a mechanism for the self-remission of tumor growth in lizards remains uncertain, but continuing study of this reptile may help uncover natural mechanisms for tumor growth inhibition.

The enhancer threshold is defined as the minimum concentration of transcription factors (TFs) required to elicit an enhancer response in a given time and space. Here, evidence is presented that the enhancer threshold is relative to promoter strength in the early Drosophila embryo. The apparently inactive even-skipped (eve) minimal stripe element (MSE), in which a single Hunchback (Hb)-binding site is deleted, is functionally complemented by the hsp70 promoter in transgenic embryos. Forced pause release of RNA polymerase II (Pol II) and transcription bubble assays show that both eve and heat shock protein 70 (hsp70) promoters exhibit paused Pol II. However, bioinformatics analyses and transient transfection assays indicate that the strength of the hsp70 promoter is much stronger than that of the eve promoter. Consistently, inactive MSE function is also restored by promoters stronger than the eve promoter. It is conceivable that the functional complementarity between enhancer and promoter strengths defines the enhancer threshold, thus determining whether a genomic locus acts as an enhancer for a particular promoter.

The Transient Receptor Potential superfamily of proteins (TRPs) form cation channels that are abundant in animal sensory systems. Amongst TRPs, the Melastatin-related family (TRPMs) is composed of members that respond to temperature, pH, sex hormones, and various other stimuli. Some TRPMs exhibit enriched expression in the gonads of vertebrate and invertebrate species, but their contributions to germline development remain to be determined. We identified twenty-one potential TRPMs in the planarian flatworm Schmidtea mediterranea and analyzed their anatomical distribution of expression by whole-mount in situ hybridization. Enriched expression of two TRPMs (Smed-TRPM-c and Smed-TRPM-l) was detected in testis, whereas eight TRPM genes had detectable expression in patterns representative of neuronal and/or sensory cell types. Functional analysis of TRPM homologs by RNA-interference (RNAi) revealed that disruption of normal levels of Smed-TRPM-c expression impaired sperm development, indicating a role for this receptor in supporting spermatogenesis. Smed-TRPM-l RNAi alone did not result in a detectable phenotype, but it did increase sperm development deficiencies when combined with Smed-TRPM-c RNAi. Fluorescence in situ hybridization revealed expression of Smed-TRPM-c in early spermatogenic cells within testes, suggesting cell-autonomous regulatory functions in germ cells for this gene. In addition, Smed-TRPM-c RNAi resulted in reduced numbers of presumptive germline stem cell clusters in asexual planarians, suggesting that Smed-TRPM-c supports the establishment, maintenance, and/or expansion of spermatogonial germline stem cells. While further research is needed to identify the factors that trigger Smed-TRPM-c activity, these findings reveal one of the few known examples for TRPM function in the direct regulation of sperm development.

The Spanish Society for Developmental Biology (SEBD) organized its 18^th meeting in October 2024 (hereafter SEBD2024), coinciding with the society's 30^th anniversary and serving as the stage for its celebrations. This article provides an overview of the event, including the speakers, scientific sessions and the different activities related to the anniversary.

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.

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 aims to analyze the pathways and the placental brain axis genes of gestational diabetes mellitus (GDM) affecting offspring neurodevelopment. Differentially expressed genes (DEGs) were identified through transcriptome sequencing of placental tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. A protein-protein interaction (PPI) network was constructed and annotated using the STRING online software. The expression of neurodevelopment-related genes was analyzed by qPCR. Hubgenes were analyzed using Cytoscape 3.7.1 software. The correlation between Hubgenes and placental brain axis genes was analyzed through literatures alignment. The pathways of GDM affecting offspring neural development were predicted using the KEGG database. The placental transcriptome revealed that there were 404 DEGs between GDM and Normal groups. Among these DEGs, 125 were upregulated and 279 were downregulated. GO analysis indicated that DEGs were mainly involved in intracellular calcium activated chloride channel activity, anion channel activity, G protein-coupled peptide receptors, etc. Additionally, KEGG analysis revealed that DEGs were predominantly involved in neuroactive ligand receptor interaction pathways. STRING online software analysis revealed that the DLGAP1, NXNL2, SCG2, SLC18A2, LYNX1, GRM1, DLGAP1, BIRC7 genes were associated with neurodevelopment. PCR validation of these 8 genes was consistent with transcriptome results (P<0.05). Literatures alignment showed that DLGAP1, GRM1 and SLC18A2 are placental brain axis genes that influence offspring neurodevelopment. The placental brain axis genes DLGAP1, GRM1, SLC18A2 have been found to influence GDM offspring neurodevelopment through the regulation of the Gq/PLC/PKC pathway.

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.