Vertebrate Organisms Research Articles

Melatonin: An Overview on the Synthesis Processes and on Its Multiple Bioactive Roles Played in Animals and Humans

Melatonin is a natural hormone synthesized mainly by the pineal gland of vertebrates, and, secondarily, by other tissues and organs as well. It is deemed a bioactive molecule due to the multiple roles and functions it performs in animals and humans. Research conducted up to 2024 has reported the presence of melatonin in a wide variety of plants and bacteria, as well. This review aims to collect some of the scientific data to identify and describe the main sources of melatonin, and to document the functions and roles it plays in animal organisms. It also includes a description of the main technological and nutritional factors that can positively or negatively influence the synthesis and secretion process of melatonin, which is subsequently transported from the animal body into some food products, such as milk. This paper also includes information on the interaction between melatonin and other bioactive compounds present in animal and human bodies, with the aim of identifying what other functions and roles this hormone performs, and whether it interacts with other substances present in the vertebrate organism.

Skin as outermost immune organ of vertebrates that elicits robust early immune responses after immunization with glycoprotein of spring viraemia of carp virus.

As the outermost immune organ in vertebrates, the skin serves as the primary interface with the external environment and plays a crucial role in initiating the early immune response. The skin contains a variety of immune cells that induce mucosal and systemic immune responses, rendering it a prime target for vaccination strategies. Insight into the mechanisms through which vaccination triggers early immune responses is paramount for advancing animal and human health, yet our current understanding remains limited. Given its significance in vertebrate evolution, teleost fish emerges as an excellent model for investigating the early immune response of skin. In this study, we demonstrate that significant quantities of vaccine can be absorbed by the skin and transported to the body through dermis and muscle metabolism by immerses immune zebrafish with glycoprotein of spring viraemia of carp virus. Immersion immunization can elicit robust and enduring immune protection, with the skin triggering a potent immune response early in the immunization process. Analysis of the skin transcriptome revealed the involvement of numerous immune-related genes in the immersion immune response, with indications that HSP70 and MAPK signals might play pivotal roles in the immune process induced by glycoprotein. Co-immunoprecipitation and cell co-localization studies confirmed the interaction between glycoprotein and HSP70. Subsequent research demonstrated that overexpression or inhibition of HSP70 could respectively enhance or impede the expression of JNK and related proteins. However, the survival rate and immune response of HSP70 inhibited zebrafish with glycoprotein treatment were significantly reduced. These findings propose that the interaction between glycoprotein and HSP70 may activate JNK, thereby modulating mucosal and systemic immune responses induced by glycoprotein. This investigation offers novel insights and a foundational understanding of early skin immune reactions.

Advancements in the Developmental Zebrafish Model for Predictive Human Toxicology.

The rapid assessment of chemical hazards to human health, with reduced reliance on mammalian testing, is essential in the 21st century. Early life stage zebrafish have emerged as a leading model in the field due to their amenability to high throughput developmental toxicity testing while retaining the benefits of using a whole vertebrate organism with high homology with humans. Zebrafish are particularly well suited for a variety of study areas that are more challenging in other vertebrate model systems including microbiome work, transgenerational studies, gene-environment interactions, molecular responses, and mechanisms of action. The high volume of data generated from zebrafish screening studies is highly valuable for QSAR modeling and dose modeling for use in predictive hazard assessment. Recent advancements and challenges in using early life stage zebrafish for predictive human toxicology are reviewed.

Molecular Characterization of Subdomain Specification of Cochlear Duct Based on Foxg1 and Gata3.

The inner ear is one of the sensory organs of vertebrates and is largely composed of the vestibule, which controls balance, and the cochlea, which is responsible for hearing. In particular, a problem in cochlear development can lead to hearing loss. Although numerous studies have been conducted on genes involved in the development of the cochlea, many areas still need to be discovered regarding factors that control the patterning of the early cochlear duct. Herein, based on the dynamic expression pattern of FOXG1 in the apical and basal regions of the E13.5 cochlear duct, we identified detailed expression regions through an open-source analysis of single-cell RNA analysis data and demonstrated a clinical correlation with hearing loss. The distinct expression patterns of FOXG1 and GATA3 during the patterning process of the cochlear duct provide important clues to understanding how the fates of the apical and basal regions are divided. These results are expected to be extremely important not only for understanding the molecular mechanisms involved in the early development of the cochlear duct, but also for identifying potential genes that cause hearing loss.

Conserved glucokinase regulation in zebrafish confirms therapeutic utility for pharmacologic modulation in diabetes

Glucokinase (GCK) is an essential enzyme for blood glucose homeostasis. Because of its importance in glucose metabolism, GCK is considered an attractive target for the development of antidiabetic drugs. However, a viable therapeutic agent has still to emerge, prompting efforts to improve understanding of the complex regulation and biological effects of GCK. Using the vertebrate organism zebrafish, an attractive model to study metabolic diseases and pharmacological responses, we dissected the complexities of gck regulation and unraveled effects of Gck modulation. We found that while gck expression in zebrafish islet cells is constitutive, gck expression in the liver is regulated by nutritional status, confirming similarity to the mammalian system. A combination of transgenic gck reporter lines and our diabetes model, the pdx1 mutant, allowed monitoring of gck expression under pathological conditions, revealing reduced gck expression and activity in the liver, which was unresponsive to nutrient stimulation, and decreased expression in the islet due to the reduced number of β-cells. Gck activation substantially ameliorated hyperglycemia in pdx1 mutants, without inducing oxidative stress responses in liver or islet. In-depth characterization of Gck activity and regulation at the cellular level in a whole-organism diabetes model clarifies its applicability as a drug target for therapies.

Bacterial Effector Screening Reveals RNF214 as a Virus Restriction Factor in Mammals.

Arboviruses are a group of arthropod-transmitted viruses that pose a significant threat to public health. Identifying host factors that inhibit arbovirus infection is critical for the development of strategies to prevent or treat these infections. Previously, we showed that bacterial effector proteins can be used as molecular tools to identify host immunity factors in insect cells that restrict arbovirus replication (Embry et al., 2024). Bacteria secrete effectors into the host cell cytoplasm to inhibit various innate immune defenses. Here, we apply our bacterial effector screening system to identify host antiviral immunity factors in two mammalian hosts - bats and humans. By screening a library of 210 effectors encoded by seven distinct bacterial pathogens, we identified three bacterial effectors (IpaH4, SopB, and SidM) that enhance the replication of both togaviruses and rhabdoviruses in bat and human cells. We also discovered several effectors that enhance arbovirus replication in a virus- or host-specific manner. We further characterize the mechanism by which the Shigella flexneri encoded E3 ubiquitin ligase, IpaH4, enhances arbovirus infection in mammalian cells. Using yeast two-hybrid, ubiquitin-activated interaction traps, in vitro ubiquitination assays and cellular approaches, we show the uncharacterized mammalian RING-domain containing protein, RNF214, to be directly targeted by IpaH4 for ubiquitination-mediated degradation. Phylogenetic analyses of RNF214 proteins indicate they are widely conserved among many vertebrate species, suggesting an important evolutionary function. We show that RNF214 overexpression suppresses arbovirus infections in a manner dependent upon its putative E3 ubiquitin ligase activity, while RNF214 depletion enhances these infections in human and bat cells. These data suggest that RNF214 proteins are important innate immune factors involved in combating viral infection. Collectively, our work shows that bacterial effectors can be useful tools for uncovering novel mammalian antiviral machinery.

Determining bad actors: A linear mixed effects model approach to elucidate behavioral toxicity of metal mixtures in drinking water

Mixtures of chemical contaminants can pose a significant health risk to humans and wildlife, even at levels considered safe for each individual chemical. There is a critical need to develop statistical methods to evaluate the drivers of toxic effects in chemical mixtures (i.e., bad actors) from exposure studies. Here, we develop a hierarchical modeling framework to disentangle the toxicity of complex metal mixtures from a screening study of 92 drinking well water samples containing multiple metal elements from Maine and New Hampshire, USA. In order to screen for neurodevelopmental impacts from exposure to these drinking water samples, we use a larval zebrafish (Danio rerio) behavioral assay. Zebrafish are an advantageous toxicological model organism due to combining the complexity of a vertebrate organism and higher-throughput exposure methods. We formulate a linear mixed modeling approach that captures intrinsic complexity in a common larval behavioral assay in order to improve its sensitivity and rigor and identify drivers of behavioral toxicity from the metal mixtures within the drinking water samples. Our analysis identifies lead (Pb), cadmium (Cd), nickel (Ni), copper (Cu), barium (Ba), and uranium (U) as metals that consistently impact larval locomotor activity, individually and across nine pairs of those metals. Our model also elucidates three distinct clusters of metal mixture components that drive behavioral effects: (Ba:Cu:U), (Ni:Pb:U), (Ba:Pb:U). Having identified a set of “bad-actor” metals from the water samples, we conduct exposure experiments for each individual metal (Pb, Cd, Ni, Cu, and Ba) at levels considered safe by the US Environmental Protection Agency drinking water regulatory limits and validate Pb, Ni, Cu, and Ba as behavioral toxicants at these concentrations. Collectively, our modeling approach estimates the impact of metal elements on a complex behavioral outcome in a statistically robust manner and establishes an approach to capture “bad actors” and key chemical interactions in a complex mixture.

Neurobehavioral and bioaccumulative toxicity in adult in-vivo zebrafish model due to prolonged cadmium exposure in the presence of ketoprofen.

Increasing industrial activity causes the release of chemical compounds into aquatic habitats, including toxic heavy metals like cadmium and medications like ketoprofen, posing considerable ecological concerns. Although previous studies have shown that cadmium and ketoprofen individually cause cognitive impairment, there is a lack of information on the combined neurological effects of the two substances. We investigated the neurological consequences of persistent cadmium exposure in the presence of ketoprofen on adult zebrafish, providing an essential model for understanding cumulative impacts on vertebrate organisms. Behavioral assessments, bioaccumulation rates, biochemical studies, and histopathological exams were conducted over 42 days in authentic environmental settings. The results of our study show that cadmium (10 µg/L) and ketoprofen (10 and 100 µg/L) at environmentally relevant concentrations had a significant impact on locomotor activity, social interactions, and cognitive responses, indicating cumulative neurotoxicity in co-exposure groups compared to single pollutant groups. Biochemical tests show disturbances in antioxidant defense systems, while histological examinations reveal structural changes in zebrafish brain regions. Ketoprofen influences cadmium accumulation in the brain, underscoring the importance of conducting complete evaluations to understand the intricate interactions between environmental pollutants. This study improves our understanding of the complex interactions between heavy metals and medications, stressing the need to consider combined exposure when assessing the neurological effects on vertebrate models.

Mutations in fibronectin dysregulate chondrogenesis in skeletal dysplasia.

Fibronectin (FN) is an extracellular matrix glycoprotein essential for the development and function of major vertebrate organ systems. Mutations in FN result in an autosomal dominant skeletal dysplasia termed corner fracture-type spondylometaphyseal dysplasia (SMDCF). The precise pathomechanisms through which mutant FN induces impaired skeletal development remain elusive. Here, we have generated patient-derived induced pluripotent stem cells as a cell culture model for SMDCF to investigate the consequences of FN mutations on mesenchymal stem cells (MSCs) and their differentiation into cartilage-producing chondrocytes. In line with our previous data, FN mutations disrupted protein secretion from MSCs, causing a notable increase in intracellular FN and a significant decrease in extracellular FN levels. Analyses of plasma samples from SMDCF patients also showed reduced FN in circulation. FN and endoplasmic reticulum (ER) protein folding chaperones (BIP, HSP47) accumulated in MSCs within ribosome-covered cytosolic vesicles that emerged from the ER. Massive amounts of these vesicles were not cleared from the cytosol, and a smaller subset showed the presence of lysosomal markers. The accumulation of intracellular FN and ER proteins elevated cellular stress markers and altered mitochondrial structure. Bulk RNA sequencing revealed a specific transcriptomic dysregulation of the patient-derived cells relative to controls. Analysis of MSC differentiation into chondrocytes showed impaired mesenchymal condensation, reduced chondrogenic markers, and compromised cell proliferation in mutant cells. Moreover, FN mutant cells exhibited significantly lower transforming growth factor beta-1 (TGFβ1) expression, crucial for mesenchymal condensation. Exogenous FN or TGFβ1 supplementation effectively improved the MSC condensation and promoted chondrogenesis in FN mutant cells. These findings demonstrate the cellular consequences of FN mutations in SMDCF and explain the molecular pathways involved in the associated altered chondrogenesis.

Article Review: Production and Purification of Antibiotics from Environmental Microorganism

The use for antibiotics to treat microbial with bacteria has been for decades a mainstay of contemporary therapy. Nevertheless, extensive antimicrobial abuse or trafficking has resulted in unforeseen effects that need significant policy reforms for prevention. Researchers discuss two major categories of implications of antimicrobial misuse and excess use in this review. Subsequently talk about how antibiotic resistance spreads from hotspot where resistance evolution occurs to the environment, having a focus on possible resistance dissemination channels. Furthermore, they describe how naturally occurring populations of microbes, in addition to crustaceans including vertebrate organisms are impacted by antimicrobial contamination; regardless of the development of susceptibility. Individuals conclude with a summary of the local initiatives that are now being implemented to mitigate the consequences of antimicrobial contamination as well as regions where these strategies are still being developed.

Understanding the Cryptosporidium species and their challenges to animal health and livestock species for informed development of new, specific treatment strategies.

Cryptosporidium species are parasitic organisms of vertebrates with a worldwide distribution. They have an important impact globally upon human and animal health, and livestock productivity. The life cycle of these species is complex and difficult to disrupt to improve human health, animal health, food security and economic growth. This may contribute to the fact that no new treatment strategy has been widely accepted or applied in livestock for years. Here we consider the natural history of these parasites, their biochemistry and economic impact. Using recent developments in understanding these parasites we then consider viable and affordable approaches to enhancing control of their effects on livestock. These are based on advances in drug discovery, omics research and artificial intelligence applications to human and veterinary medicine that indicate putative new therapeutic approaches.

ViSCNOVAS: A Novel Classification System for Hyaluronic Acid-Based Gels in Orthobiologic Products and Regenerative Medicine.

Hyaluronic acid (HA), a naturally occurring polysaccharide, holds immense potential in regenerative medicine due to its diverse biological functions and clinical applications, particularly in gel formulations. This paper presents a comprehensive exploration of HA, encompassing its origins, molecular characteristics, and therapeutic roles in gel-based interventions. Initially identified in bovine vitreous humor, HA has since been found in various tissues and fluids across vertebrate organisms and bacterial sources, exhibiting consistent physicochemical properties. The synthesis of HA by diverse cell types underscores its integral role in the extracellular matrix and its relevance to tissue homeostasis and repair. Clinical applications of HA, particularly in addressing musculoskeletal ailments such as osteoarthritis, are examined, highlighting its efficacy and safety in promoting tissue regeneration and pain relief. Building upon this foundation, a novel classification system for HA-based interventions is proposed, aiming to standardize treatment protocols and optimize patient outcomes. The ViSCNOVAS classification system refers to viscosity, storage, chain, number, origin, volume, amount, and size. This classification is specifically designed for HA-based orthobiologic products used in regenerative medicine, including orthopedics, sports medicine, aesthetics, cosmetic dermatology, and wound healing. It aims to provide clinicians with a structured framework for personalized treatment strategies. Future directions in HA research are also discussed, emphasizing the need for further validation and refinement of the proposed classification system to advance the field of regenerative medicine. Overall, this manuscript elucidates the biological functions of hyaluronic acid and its potential in clinical practice while advocating for standardization to enhance patient care in various regenerative applications.

BirthSeq, a new method to isolate and analyze dated cells in different vertebrates.

Embryonic development is a complex and dynamic process that unfolds over time and involves the production and diversification of increasing numbers of cells. The impact of developmental time on the formation of the central nervous system is well documented, with evidence showing that time plays a crucial role in establishing the identity of neuronal subtypes. However, the study of how time translates into genetic instructions driving cell fate is limited by the scarcity of suitable experimental tools. We introduce BirthSeq, a new method for isolating and analyzing cells based on their birth date. This innovative technique allows for in vivo labeling of cells, isolation via fluorescence-activated cell sorting, and analysis using high-throughput techniques. We calibrated the BirthSeq method for developmental organs across three vertebrate species (mouse, chick and gecko), and utilized it for single-cell RNA sequencing and novel spatially resolved transcriptomic approaches in mouse and chick, respectively. Overall, BirthSeq provides a versatile tool for studying virtually any tissue in different vertebrate organisms, aiding developmental biology research by targeting cells and their temporal cues.

Distinct molecular profile of the chick organizer as a stem zone during axial elongation.

The vertebrate organizer plays a crucial role in building the main (antero-posterior) axis of the embryo: it neuralizes the surrounding ectoderm, and is the site of emigration for cells making axial and paraxial mesendoderm during elongation. The chick organizer becomes a stem zone at the onset of elongation; it stops recruiting cells from the neighbouring ectoderm and generates all its derivatives from the small number of resident cells it contains at the end of gastrulation stages. Nothing is known about the molecular identity of this stem zone. Here, we specifically labelled long-term resident cells of the organizer and compared their RNA-seq profile to that of the neighbouring cell populations. Screening by reverse transcription-polymerase chain reaction and in situ hybridization identified four genes (WIF1, PTGDS, ThPO and UCKL1) that are upregulated only in the organizer region when it becomes a stem zone and remain expressed there during axial elongation. In experiments specifically labelling the resident cells of the mature organizer, we show that only these cells express these genes. These findings molecularly define the organizer as a stem zone and offer a key to understanding how this zone is set up, the molecular control of its cells' behaviour and the evolution of axial growth zones.

Different stressors uniquely affect the expression of endocannabinoid-metabolizing enzymes in the central ring ganglia of Lymnaea stagnalis.

The endocannabinoid system (ECS) plays an important role in neuroprotection, neuroplasticity, energy balance, modulation of stress, and inflammatory responses, acting as a critical link between the brain and the body's peripheral regions, while also offering promising potential for novel therapeutic strategies. Unfortunately, in humans, pharmacological inhibitors of different ECS enzymes have led to mixed results in both preclinical and clinical studies. As the ECS has been highly conserved throughout the eukaryotic lineage, the use of invertebrate model organisms like the pond snail Lymnaea stagnalis may provide a flexible tool to unravel unexplored functions of the ECS at the cellular, synaptic, and behavioral levels. In this study, starting from the available genome and transcriptome of L. stagnalis, we first identified putative transcripts of all ECS enzymes containing an open reading frame. Each predicted protein possessed a high degree of sequence conservation to known orthologues of other invertebrate and vertebrate organisms. Sequences were confirmed by qualitative PCR and sequencing. Then, we investigated the transcriptional effects induced by different stress conditions (i.e., bacterial LPS injection, predator scent, food deprivation, and acute heat shock) on the expression levels of the enzymes of the ECS in Lymnaea's central ring ganglia. Our results suggest that in Lymnaea as in rodents, the ECS is involved in mediating inflammatory and anxiety-like responses, promoting energy balance, and responding to acute stressors. To our knowledge, this study offers the most comprehensive analysis so far of the ECS in an invertebrate model organism.

Neural crest development and disorders: from patient to model system and back again - the NEUcrest conference.

The neural crest (NC) is an embryonic multipotent and transitory population of cells that appears during late gastrulation/early neurulation in the developing embryos of vertebrate organisms. Often called "the fourth germ layer", the NC is characterised by incredible mobility, which allows the NC cells to migrate throughout the whole embryo, giving rise to an astonishing number of different derivatives in the adult organism, such as craniofacial skeleton, adrenal gland, enteric nervous system and melanocytes. Because of these properties, neurocristopathies (NCPs), which is the term used to classify genetic diseases associated with NC developmental defects, are often syndromic and, taken all together, are the most common type of genetic disease. The NEUcrest consortium is an EU funded innovative training network (ITN) that aims to study the NC and NCPs. In March 2024, the early stage researchers (ESRs) in the NEUcrest consortium organised an in-person conference for well-established and early career researchers to discuss new advances in the NC and NCPs field, starting from the induction of the NC, and then moving on to migration and differentiation processes they undergo. The conference focused heavily on NCPs associated with each of these steps. The conference also included events, such as a round table to discuss the future of the NC research, plus a talk by a person living with an NCP. This 3-day conference aimed to bring together the past, present and future of this field to try and unravel the mysteries of this unique cell population.

Pulmonary arteries in coelacanths shed light on the vasculature evolution of air-breathing organs in vertebrates

To date, the presence of pulmonary organs in the fossil record is extremely rare. Among extant vertebrates, lungs are described in actinopterygian polypterids and in all sarcopterygians, including coelacanths and lungfish. However, vasculature of pulmonary arteries has never been accurately identified neither in fossil nor extant coelacanths due to the paucity of fossil preservation of pulmonary organs and limitations of invasive studies in extant specimens. Here we present the first description of the pulmonary vasculature in both fossil and extant actinistian, a non-tetrapod sarcopterygian clade, contributing to a more in-depth discussion on the morphology of these structures and on the possible homology between vertebrate air-filled organs (lungs of sarcopterygians, lungs of actinopterygians, and gas bladders of actinopterygians).

Tail and Spinal Cord Regeneration in Urodelean Amphibians.

Urodelean amphibians can regenerate the tail and the spinal cord (SC) and maintain this ability throughout their life. This clearly distinguishes these animals from mammals. The phenomenon of tail and SC regeneration is based on the capability of cells involved in regeneration to dedifferentiate, enter the cell cycle, and change their (or return to the pre-existing) phenotype during de novo organ formation. The second critical aspect of the successful tail and SC regeneration is the mutual molecular regulation by tissues, of which the SC and the apical wound epidermis are the leaders. Molecular regulatory systems include signaling pathways components, inflammatory factors, ECM molecules, ROS, hormones, neurotransmitters, HSPs, transcriptional and epigenetic factors, etc. The control, carried out by regulatory networks on the feedback principle, recruits the mechanisms used in embryogenesis and accompanies all stages of organ regeneration, from the moment of damage to the completion of morphogenesis and patterning of all its structures. The late regeneration stages and the effects of external factors on them have been poorly studied. A new model for addressing this issue is herein proposed. The data summarized in the review contribute to understanding a wide range of fundamentally important issues in the regenerative biology of tissues and organs in vertebrates including humans.

Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms.

The review presents a detailed discussion of the evolving field studying interactions between ionic liquids (ILs) and biological systems. Originating from molten salt electrolytes to present multiapplication substances, ILs have found usage across various fields due to their exceptional physicochemical properties, including excellent tunability. However, their interactions with biological systems and potential influence on living organisms remain largely unexplored. This review examines the cytotoxic effects of ILs on cell cultures, biomolecules, and vertebrate and invertebrate organisms. Our understanding of IL toxicity, while growing in recent years, is yet nascent. The established findings include correlations between harmful effects of ILs and their ability to disturb cellular membranes, their potential to trigger oxidative stress in cells, and their ability to cause cell death via apoptosis. Future research directions proposed in the review include studying the distribution of various ILs within cellular compartments and organelles, investigating metabolic transformations of ILs in cells and organisms, detailed analysis of IL effects on proteins involved in oxidative stress and apoptosis, correlation studies between IL doses, exposure times and resulting adverse effects, and examination of effects of subtoxic concentrations of ILs on various biological objects. This review aims to serve as a critical analysis of the current body of knowledge on IL-related toxicity mechanisms. Furthermore, it can guide researchers toward the design of less toxic ILs and the informed use of ILs in drug development and medicine.

Morphogenetic Promoters in the Development of Provisional and Definitive Urinary Organs in Humans and Vertebrates

The aim is to show the regulatory significance of promoter organs of morphogenesis in a stable state of the kidneys of vertebrates (fish, birds) and humans. Material and methods. 118 embryos at stages 12-23 of Carnegie (SC) and 28 human fetuses of 9-12 weeks of fetogenesis, 268 embryos of meat chickens (cross "Hibro PG +") from the stage of 48 hours to 20 days of broiler egg incubation, 50 fry of peled Coregonus peled were studied (Gmelin, 1788) at the stage of yolk sac atrophy (stage 36-37 according to the classification of Detlaf, 1975). To study the method of light microscopy, the material fixed in a 10% neutral form, embedded in paraffin. Sections stained with Mayer's hematoxylin and eosin, McManus CHIC method. Ki-67, CD31, CD34, positive cells are detected by immunohistochemistry. Primary kidney examination by low-vacuum electron microscopy. Embryos and human fetuses are observed in the Tyumen health care facility during medical abortion on demand in anamnestic healthy women with their warning about emergency work. Observation chicken embryos at the poultry farm “Tyumensky Broiler”, incubation workshop (Kaskara village, Tyumen region). Morphometric analysis and statistical processing of the actual material were carried out. Results. It was shown that the organotypic differentiation of the intermediate mesenchyme and the formation of nephrons of the provisional and definitive urinary organs control the state of the mesonephric duct and metanephritic diverticulum. The mesonephric duct initiates the organotypic antibiotic of the perifocal intermediate mesonephric mesenchyme and detects the proximodistal vector of saltatory mesonephronogenesis. The metanephritic diverticulum and its daughter branches initiate the organotypic differentiation of the intermediate mesenchyme and control the fan mechanism of metanephronogenesis. Activity of nephronogenesis Determination of the dynamics of convergence of immunocompetent cells. The absence of ventrodorsal generation of mesonephrons in humans is associated with a significant vital cycle of a normal kidney, atrophy of the mesonephric duct, and a decrease in the activity of immunocompetent cells. An increase in the expression of CD31, CD34, Bcl-2, Ki-67 positive cells is realized in combination with the formation of nephron rudiments as the promoter organs move in the developing organ of urinary formation. Conclusion. Prenatal organogenesis monitors and constantly monitors the formation of promoter organs of morphogenesis - the mesonephric duct and the metanephric disserticulum. Organotypic infection of the intermediate mesenchyme during the development of fish, birds and humans correlates with the chronovector of the convergence of immunocompetent cells.