Embryonic Origin Research Articles

Thinning of central foveal thickness in the retina of patients with schizophrenia.

The neural retina shares a common embryonic origin with the brain and yields pathological changes like that in the brain in various neuropsychiatric disorders, including schizophrenia. Non-invasive examination by optical coherence tomography (OCT) revealed retinal structure abnormalities in patients with schizophrenia. This study investigated retina structures in 29 patients with schizophrenia and 25 healthy controls in a Chinese Han ethnic population with spectral domain OCT. Measurements of central foveal thickness (CFT) as well as other retinal structures in macular and peripapillary subregions were performed. Associations between OCT parameters and clinical features, including severity of positive and negative symptoms, disease duration and antipsychotic dosage were analyzed. With controlling for age and sex, patients showed significantly thinner CFT, thinner central macular thickness, and thinner total retinal thickness in subregions of the central, inner superior, inner temporal, and inner nasal macula of both eyes, thinner ganglion cell complex in a subregion of the left eye, as well as larger cup volume in the peripapillary region of the right eye. In addition, CFT also negatively correlated with severity of negative symptoms. These findings suggest that CFT has the potential to be a disease biomarker of schizophrenia.

Radial Longitudinal Deficiency: New Perspectives on an Enduring Challenge.

Radial longitudinal deficiency (RLD) is a multidimensional congenital hand difference encompassing skeletal, musculotendinous, and joint components. Managing RLD remains challenging, with numerous surgical procedures over the past century failing to achieve a stable, mobile, growing wrist without recurrence of the deformity. This review investigates new therapeutic approaches for RLD, delving into genetic, embryological, and histological aspects, including proximal muscle involvement and causes of recurrence.A notable association between RLD and preaxial polydactyly, linked to aberrations in the Sonic Hedgehog signaling pathway, is highlighted, suggesting a common embryonic origin. Experimental evidence indicates that ectopic Sonic Hedgehog signaling can result in radial aplasia and preaxial polydactyly. Histopathological studies revealed significant muscle abnormalities in RLD, contributing to deformities and recurrences.Techniques such as preoperative soft tissue distraction show promise, but recurrence rates persist. Alternative surgical procedures, such as vascularized second metatarsophalangeal joint transfer and ulna cuff osteotomy, offer potential improvements by minimizing recurrence and optimizing limb length.Despite advancements, effective management of RLD requires further research into the interplay between genetic factors, muscle abnormalities, and surgical outcomes. This review underscores the importance of early detection, genetic counseling, and a multidisciplinary approach to enhance long-term functional and aesthetic results for RLD patients.

Identification of novel nutrient sensitive human yolk sac functions required for embryogenesis

The human yolk sac (hYS) is essential for embryo nutrient biosynthesis/transport and development. However, there lacks a comprehensive study of hYS nutrient-gene interactions. Here we performed a secondary analysis of hYS transcript profiles (n = 9 samples) to identify nutrient-sensitive hYS genes and regulatory networks, including those that associate with adverse perinatal phenotypes with embryonic origins. Overall, 14.8% highly expressed hYS genes are nutrient-sensitive; the most common nutrient cofactors for hYS genes are metals and B vitamins. Functional analysis of highly expressed hYS genes reveals that nutrient-sensitive hYS genes are more likely to be involved in metabolic functions than hYS genes that are not nutrient-sensitive. Through nutrient-sensitive gene network analysis, we find that four nutrient-sensitive transcription regulators in the hYS (with zinc and/or magnesium cofactors) are predicted to collectively regulate 30.9% of highly expressed hYS genes. Lastly, we identify 117 nutrient-sensitive hYS genes that associate with an adverse perinatal outcome with embryonic origins. Among these, the greatest number of nutrient-sensitive hYS genes are linked to congenital heart defects (n = 54 genes), followed by microcephaly (n = 37). Collectively, our study characterises nutrient-sensitive hYS functions and improves understanding of the ways in which nutrient-gene interactions in the hYS may influence both typical and pathological development.

ASPECTOS DE IMAGEM NO HEPATOBLASTOMA: REVISÃO DE LITERATURA.

Hepatoblastoma (HB) is a considerably rare primary malignant liver neoplasm of embryonic origin, and the most prevalent hepatic carcinoma among children, primarily affecting individuals under five years old. Objective: to investigate the prevalence and characteristics of imaging findings in hepatoblastoma described in the scientific literature between 2019 and 2024. Method: A literature review was conducted in the PubMed, Scopus, Web of Science, and SciELO databases over the past 5 years. Results and Discussion: Nine studies were found, predominantly on computed tomography and abdominal ultrasound. The morphological patterns presented in the imaging aspects by USG, CT, and MRI differ between the methods, highlighting the complexity of hepatoblastoma and the variability of presentation in imaging examinations. However, all studies demonstrated the importance of imaging methods in staging and defining tumor resectability criteria. Conclusion: There is a scarcity of studies on the imaging findings of Hepatoblastoma, as well as the variety of imaging characteristics in the different evaluated methods. The importance of using imaging methods for the adequate staging of hepatoblastoma and consequent definition of therapeutic conduct is also highlighted.

Dextrocardia and Pseudodextrocardia: Dextroversion and Dextroinversion! What Do You Need to Know in Clinical Practice?

Dextrocardia is a rare condition characterized by the location of the heart on the right side of the thoracic cavity instead of the left side; it is a congenital pathology whose embryonic origin is not known to date. This is a case of situs inversus totalis in a 30-year-old woman who presented to routine cardiology with symptoms of atypical thoracic co-occurring cough and abdominal pain. CT scan of the abdomen and ultrasound are not enough to reverse organs caused by hemorrhage. This case is reported to illustrate the imaging of dextrocardia and highlight its implications for clinical thoracic radiology and echocardiogram practice. This case also adds to the growing body of global literature on the context of this birth defect in our environment.

Giant Cervical Teratoma In Adults: Case Report

Teratomas are tumours of embryonic origin, most commonly found in the sacrum and coccyx. Localisation in the neck is rare, occurring in only 3% of cases, with a high mortality rate of up to 80% in the neonatal period as a result of airway obstruction. Immaturity is not a sign of malignancy when the tumour is managed during the neonatal period. We will report a case of a patient diagnosed and treated in the otorhinolaryngology surgery department of the Hassan II military hospital in LAAYOUNE, highlighting the fact that there is still a lack of antenatal screening, despite improvements in the management of newborns

Placental Evolution: Innovating How to Feed Babies.

The evolution of the placenta was transformative. It changed how offspring are fed during gestation from depositing all the resources into an egg to continually supplying resources throughout gestation. Placental evolution is infinitely complex, with many moving parts, but at the core it is driven by a conflict over resources between the mother and the baby, which sets up a Red Queen race, fueling rapid diversification of morphological, cellular, and genetic forms. Placentas from even closely related species are highly divergent in form and function, and many cellular processes are distinct. If we could extract the entirety of genomic information for placentas across all species, including the many hundreds that have evolved in fish and reptiles, we could find their shared commonality, and that would tell us which of the many pieces really matter. We do not have this information, but we do have clues. Convergent evolution mechanisms were repeatedly used in the placenta, including the intense selective pressure to co-opt an envelope protein to build a multinucleated syncytium, the use of the same hormones and structural proteins in placentas derived from separate embryonic origins that arose hundreds of millions of years apart, and the co-option of endogenous retroviruses to form capsids as a way of transport and as mutagens to form new enhancers. As a result, the placental genome is the Wild West of biology, set up to rapidly change, adapt, and innovate. This ability to adapt facilitated the evolution of big babies with big brains and will continue to support offspring and their mothers in our ever-changing global environment.

Single-cell RNA transcriptomics in mice reveals embryonic origin of fibrosis due to maternal obesity

Over 40% of pregnant women in the USA are obese which negatively affects fetal development and offspring health. Maternal obesity (MO) leads to fibrotic infiltration in multiple tissues and organs of offspring during their adulthood although the origin and mechanisms are unclear. C57BL/6J female mice were fed a control and high-fat diet to mimic MO condition. Embryonic somatic tissues were obtained at E9.5, E11.5, and E13.5 (equivalent to 6 weeks of human pregnancy) from control (CON) and MO mice for single-cell RNA-sequencing (scRNA-seq). To explore the role of AMP-activated protein kinase (AMPK), AMPK was activated by metformin and A769662, and knocked out in embryonic mesenchymal cells (EMC) using AMPKα1 floxed mice. Using unsupervised clustering, we identified three major cell populations with fibrogenic capacity. Compared to CON, the population of fibrogenic cells increased dramatically (by ∼125%) due to MO, supporting an embryonic origin of fibrosis in the offspring. MO induced inflammatory response and elevated expression of transforming growth factor β (TGFβ) signalling and fibrogenic genes in embryos. MO inhibited AMPK and its activation by metformin and A769662 inhibited TGFβ signalling and fibrogenesis. MO profoundly enhances embryonic fibrogenesis, explaining the origin of fibrosis in the offspring of mothers living with obesity. Our data underscore the importance of early intervention, before 5-6 weeks of pregnancy, in improving embryonic development, and AMPK is an amiable target for suppressing excessive fibrogenesis in MO embryos to assist increasing populations of obese mothers having healthy children. This work was funded by National Institutes of Health Grant R01HD067449.

Embryonic Development of the Gastrodermis in the Coral Acropora tenuis.

Due to limited spawning seasons, embryogenesis of corals has not fully been studied and the embryonic origin of gastrodermis remains uncertain in Acropora. We herein examined how embryonic endodermal cells develop into the gastrodermis and mesentery of polyps in Acropora tenuis. In juvenile polyps, the gastrodermis invaginates to form mesenteries, both of which were stained with rhodamine-phalloidin, an anti-myocyte-specific enhancer factor 2 (anti-AtMef2) antibody, and an anti-lipoxygenase homology domain-containing protein 1 (anti-AtLoxhd1) antibody. Rhoda-mine-phalloidin staining was traced back to the endodermal cells of 60-85 hpf 'pear'-stage embryos through the larval stage. AtMef2 appeared in the blastomeres of a 12-hpf 'prawnchip'-stage embryo that was a variant U-shaped blastula with a narrow blastocoel. AtMef2 temporarily disappeared from the nuclei of 28-hpf 'donut'-stage embryos and reappeared in the endodermal cells of 40-hpf early 'pear'-stage embryos, suggesting a transition from maternal to zygotic expression of Mef2. The blastopore closed without the invagination of blastomeres. The gastrocoel collapsed and the Mef2-positive endoderm was dissociated into single cells in the well-developed blastocoel filled with yolk cells. The mesoglea appeared in the yolk cell layer. AtLoxhd1 was traced back to the endodermal cells of 'pear'-stage embryos. In 11-dpf larvae, Loxhd1-positive endodermal cells elongated in the vicinity of the mesoglea to adhere to each other and form the gastroderm epithelium in larvae. Therefore, in this coral, the inner wall of U-shaped early embryos is the cellular origin of the gastrodermis. Inner wall-derived endodermal cells move independently toward the mesoglea, where cell-cell adhesion occurs to establish the gastrodermis.

Zebrafish arterial valve development occurs through direct differentiation of second heart field progenitors.

Bicuspid Aortic Valve (BAV) is the most common congenital heart defect, affecting at least 2% of the population. The embryonic origins of BAV remain poorly understood, with few assays for validating patient variants, limiting the identification of causative genes for BAV. In both human and mouse, the left and right leaflets of the arterial valves arise from the outflow tract cushions, with interstitial cells originating from neural crest cells and the overlying endocardium through endothelial-to-mesenchymal transition (EndoMT). In contrast, an EndoMT-independent mechanism of direct differentiation of cardiac progenitors from the second heart field (SHF) is responsible for the formation of the anterior and posterior leaflets. Defects in either of these developmental mechanisms can result in BAV. Although zebrafish have been suggested as a model for human variant testing, their naturally bicuspid arterial valve has not been considered suitable for understanding human arterial valve development. Here, we have set out to investigate to what extent the processes involved in arterial valve development are conserved in zebrafish and ultimately, whether functional testing of BAV variants could be carried out. Using a combination of live imaging, immunohistochemistry and Cre-mediated lineage tracing, we show that the zebrafish arterial valve primordia develop directly from SHF progenitors with no contribution from EndoMT or neural crest, in keeping with the human and mouse anterior and posterior leaflets. Moreover, once formed, these primordia share common subsequent developmental events with all three aortic valve leaflets. Our work highlights a conserved ancestral mechanism of arterial valve leaflet formation from the SHF and identifies that development of the arterial valve is distinct from that of the atrioventricular valve in zebrafish. Crucially, this confirms the utility of zebrafish for understanding the development of specific BAV subtypes and arterial valve dysplasia, offering potential for high-throughput variant testing.

MrgprC11+ Jugular Neurons Control Airway Hyperresponsiveness in Allergic Airway Inflammation.

The lung is densely innervated by sensory nerves, the majority of which are derived from the vagal sensory neurons. Vagal ganglia consist of two different ganglia, termed nodose and jugular ganglia, with distinct embryonic origins, innervation patterns, and physiological functions in the periphery. Since nodose neurons constitute the majority of the vagal ganglia, our understanding of the function of jugular nerves in the lung is very limited. This study aims to investigate the role of MrgprC11+ jugular sensory neurons in a mouse allergic asthma model. Our previous study has shown that MrgprC11+ jugular neurons mediate cholinergic bronchoconstriction. In this study, we found that in addition to MrgprC11, several other Mrgpr family members including MrgprA3, MrgprB4, and MrgprD are also specifically expressed in the jugular sensory neurons. MrgprC11+ jugular neurons exhibit dense innervation in the respiratory tract including the larynx, trachea, proximal, and distal bronchus. We also found that receptors for IL-4 and oncostatin M, two critical cytokines promoting allergic airway inflammation, are mainly expressed in jugular sensory neurons. Both IL-4 and oncostatin M can sensitize the neuronal responses of MrgprC11+ jugular neurons. Moreover, ablation of MrgprC11+ neurons significantly inhibited airway hyperresponsiveness in the asthmatic lung, demonstrating the critical role of MrgprC11+ neurons in controlling airway constriction. Our results emphasize the critical role of jugular sensory neurons in respiratory diseases.

Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and Shadows

Background: T1D is a severe metabolic disorder due to selective autoimmune pancreatic islet β-cell killing, which results in complete abrogation of endogenous insulin secretion. The affected patients, once the disease is clinically overt, must immediately undertake insulin supplementation according to intensive therapy regimens to prevent the onset of acute and chronic complications, some of them potentially lethal. Replacement of the destroyed β-cells with fresh and vital pancreatic endocrine tissue, either of the whole organ or isolated islets transplantation, started a few decades ago with progressively encouraging results, although exogenous insulin withdrawal was obtained in a minor cohort of the treated patients. The restricted availability of donor organs coupled with general immunosuppression treatment of recipients to avoid graft immune rejection may, at least partially, explain the limited success achieved by these procedures. Results: The introduction of pluripotent stem cells (either of human embryonic origin or adult cells genetically induced to pluripotency) that can be differentiated toward insulin secretory β-like cells could provide an indefinite resource for insulin-producing cells (IPCs). Conclusions: Because the use of human embryos may encounter ethical problems, employment of adult multipotent mesenchymal stem cells (MSCs) extracted from several tissues may represent an alternative option. MSCs are associated with strong immunoregulatory properties that can alter early stages of β-cell-directed autoimmunity in T1D, other than holding the potential to differentiate themselves into β-like cells. Lights and shadows of these new strategies for the potential cure of T1D and their advancement state are reviewed.

PDOC-01 THERAPEUTIC DIFFICULTY IN THE MANAGEMENT OF A RECURRENT CRANIOPHARYNGIOMA IN A CHILD: REVIEW OF THE LITERATURE AND CASE REPORT

Abstract BACKGROUND Craniopharyngiomas are rare, benign epithelial tumors of embryonic origin in children that develop along the craniopharyngeal duct from Rathke’s pouch. The optimal treatment algorithm remains challenging. We report a child case of recurrent craniopharyngioma with therapeutic challenges. CASE PRESENTATION 12-year-old patient, followed for a multi-operated type 2 craniopharyngioma (December 2017, November 2018, and April 2022), stroke on left sylvian stenosis with right hemiplegia in 2020 during proton therapy (52 Gray), thrombolysed with good recovery after rehabilitation, sequellar panhypopituitarism. He was seen in consultation for visual field deterioration. Clinical examination showed a conscious, coherent, obese patient with a deteriorating visual field. Ophthalmological examination showed visual acuity 10/10 with slight temporal visual field amputation on the left and monocular blindness on the right due to probable optic atrophy sequelae of the craniopharyngioma. Magnetic resonance imaging revealed progression of the residual multicystic lesion in the sellar and left temporal regions, entering the sylvian valley and severely compressing the optic pathways. The tumor was removed under general anesthetic in a supine position, with release of the optic nerve, the carotid artery, and its division, and the left 3rd cranial nerve. The postoperative course is straightforward. CONCLUSION Morbidity and the assessment of sequelae are now at the forefront of the management of craniopharyngiomas. The current therapeutic approach should be reconsidered, in terms of the indications for surgery and the surgical protocol. This patient’s case is a typical example of the therapeutic difficulties involved in the management of craniopharyngiomas.

Resilience of dermis resident macrophages to inflammatory challenges.

The skin serves as a complex barrier organ populated by tissue-resident macrophages (TRMs), which play critical roles in defense, homeostasis, and tissue repair. This review examines the functions of dermis resident TRMs in different inflammatory settings, their embryonic origins, and their long-term self-renewal capabilities. We highlight the M2-like phenotype of dermal TRMs and their specialized functions in perivascular and perineuronal niches. Their interactions with type 2 immune cells, autocrine cytokines such as IL-10, and their phagocytic clearance of apoptotic cells have been explored as mechanisms for M2-like dermal TRM self-maintenance and function. In conclusion, we address the need to bridge murine models with human studies, with the possibility of targeting TRMs to promote skin immunity or restrain cutaneous pathology.

Ventral body wall closure: Mechanistic insights from mouse models and translation to human pathology.

The ventral body wall (VBW) that encloses the thoracic and abdominal cavities arises by extensive cell movements and morphogenetic changes during embryonic development. These morphogenetic processes include embryonic folding generating the primary body wall; the initial ventral cover of the embryo, followed by directed mesodermal cell migrations, contributing to the secondary body wall. Clinical anomalies in VBW development affect approximately 1 in 3000 live births. However, the cell interactions and critical cellular behaviors that control VBW development remain little understood. Here, we describe the embryonic origins of the VBW, the cellular and morphogenetic processes, and key genes, that are essential for VBW development. We also provide a clinical overview of VBW anomalies, together with environmental and genetic influences, and discuss the insight gained from over 70 mouse models that exhibit VBW defects, and their relevance, with respect to human pathology. In doing so we propose a phenotypic framework for researchers in the field which takes into account the clinical picture. We also highlight cases where there is a current paucity of mouse models for particular clinical defects and key gaps in knowledge about embryonic VBW development that need to be addressed to further understand mechanisms of human VBW pathologies.

Astrocyte allocation during brain development is controlled by Tcf4-mediated fate restriction

Astrocytes in the brain exhibit regional heterogeneity contributing to regional circuits involved in higher-order brain functions, yet the mechanisms controlling their distribution remain unclear. Here, we show that the precise allocation of astrocytes to specific brain regions during development is achieved through transcription factor 4 (Tcf4)-mediated fate restriction based on their embryonic origin. Loss of Tcf4 in ventral telencephalic neural progenitor cells alters the fate of oligodendrocyte precursor cells to transient intermediate astrocyte precursor cells, resulting in mislocalized astrocytes in the dorsal neocortex. These ectopic astrocytes engage with neocortical neurons and acquire features reminiscent of dorsal neocortical astrocytes. Furthermore, Tcf4 functions as a suppressor of astrocyte fate during the differentiation of oligodendrocyte precursor cells derived from the ventral telencephalon, thereby restricting the fate to the oligodendrocyte lineage in the dorsal neocortex. Together, our findings highlight a previously unappreciated role for Tcf4 in regulating astrocyte allocation, offering additional insights into the mechanisms underlying neurodevelopmental disorders linked to Tcf4 mutations.

Advances in retinal imaging biomarkers for the diagnosis of cerebrovascular disease.

The increasing incidence and mortality rates of cerebrovascular disease impose a heavy burden on both patients and society. Retinal imaging techniques, such as fundus photography, optical coherence tomography, and optical coherence tomography angiography, can be used for rapid, non-invasive evaluation of cerebral microcirculation and brain function since the retina and the central nervous system share similar embryonic origin characteristics and physiological features. This article aimed to review retinal imaging biomarkers related to cerebrovascular diseases and their applications in cerebrovascular diseases (stroke, cerebral small vessel disease [CSVD], and vascular cognitive impairment [VCI]), thus providing reference for early diagnosis and prevention of cerebrovascular diseases.

Metastatic brainstem medulloblastoma: a clinical case report

Medulloblastoma (MB) is one of the most common tumors of the central nervous system (CNS) of embryonic origin. MB is a malignancy that is quite common in pediatric patients; it represents a small proportion of brain tumors in young people, with an incidence of 0.6 per million per year. The peak age of diagnosis among the pediatric population is 3-6 years, while patients between 15 and 44 years old account for only 25%. The purpose of the study: to demonstrate a clinical case of surgical treatment of a patient with CNS metastasis of brainstem medulloblastoma. Methods. The article presents our clinical case of surgical treatment of a patient with medulloblastoma metastasis to the right temporal lobe. Results. Medulloblastoma is a heterogeneous brain tumor that is very rare in adults, especially those over 40 years of age, and accounts for less than 1% of all primary brain tumors in adults. Medulloblastoma metastases are most often found in the spinal cord and its membranes, less often in the cerebral hemispheres and ventricular system, which is associated with cerebrospinal fluid pathways. In foreign and Russian literature, there are relatively few publications on studies of metastatic lesions of medulloblastoma in adults; these studies are either considered as separate clinical observations or in conjunction with the development of medulloblastoma metastases in children. Non-specific neurological symptoms of medulloblastoma in adults can lead to later instrumental studies and specific therapy, and can also act as an unfavorable prognostic factor for the disease. Conclusion. Early detection and neurosurgical intervention are the key to preventing mortality and improving patient outcomes. Currently, only a few cases of medulloblastoma in adults are known; to prevent patient mortality, more detailed genetic and molecular studies of MB, including cerebrospinal fluid, risk stratification, description of oncological treatment, and monitoring of results to analyze MB sensitivity to chemotherapy and EBRT, as well as maintaining a registry of patients over 18 years old with brain medulloblastoma and dynamic observation of their family members in connection with oncological vigilance are needed.

Embryonic origins of forebrain oligodendrocytes revisited by combinatorial genetic fate mapping.

Multiple embryonic origins give rise to forebrain oligodendrocytes (OLs), yet controversies and uncertainty exist regarding their differential contributions. We established intersectional and subtractional strategies to genetically fate map OLs produced by medial ganglionic eminence/preoptic area (MGE/POA), lateral/caudal ganglionic eminences (LGE/CGE), and dorsal pallium in the mouse brain. We found that, contrary to the canonical view, LGE/CGE-derived OLs make minimum contributions to the neocortex and corpus callosum, but dominate piriform cortex and anterior commissure. Additionally, MGE/POA-derived OLs, instead of being entirely eliminated, make small but sustained contribution to cortex with a distribution pattern distinctive from those derived from the dorsal origin. Our study provides a revised and more comprehensive view of cortical and white matter OL origins, and established valuable new tools and strategies for future OL studies.

Embryonic origins of forebrain oligodendrocytes revisited by combinatorial genetic fate mapping

Embryonic origins of forebrain oligodendrocytes revisited by combinatorial genetic fate mapping