The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Positional information plays a crucial role in embryonic pattern formation, yet its role in tooth development remains unexplored. In this study, we investigated the regional specification of lingual and buccal dental mesenchyme during tooth development. Tooth germs at the cap stage were dissected from mouse mandibles, and their lingual and buccal mesenchymal regions were separated for bulk RNA sequencing. Gene ontology analysis revealed that odontogenesis, pattern specification, and proliferation-related genes were enriched in the lingual mesenchyme, whereas stem cell development, mesenchymal differentiation, neural crest differentiation, and regeneration-related genes were predominant in the buccal mesenchyme. Reaggregation experiments using Wnt1^creERT/+; R26R^tdT/+ and WT mouse models demonstrated that lingual mesenchyme contributes to tooth formation, while buccal mesenchyme primarily supports surrounding tissues. Furthermore, only the lingual part of tooth germs exhibited odontogenic potential when cultured in vitro and transplanted under the kidney capsule. Bulk RNA transcriptomic analysis further validated the regional specification of the lingual and buccal mesenchyme. These findings provide novel insights into the molecular basis of positional information in tooth development and pattern formation.
Animals ; Mice ; Odontogenesis/genetics* ; Tooth Germ/cytology* ; Mesoderm/cytology* ; Cell Differentiation ; Mesenchymal Stem Cells ; Tooth/embryology*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Mechanical stimulus is critical to cardiovascular development during embryogenesis period.The mechanoreceptors of endocardial cells and cardiac myocytes may sense mechanical signals and initiate signal transduction that induce gene expression at a cellular level,and then translate molecular-level events into tissue-level deformations,thus guiding embryo development.This review summarizes the regulatory roles of mechanical signals in the early cardiac development including the formation of heart tube,looping,valve and septal morphogenesis,ventricular development and maturation.Further,we discuss the potential mechanical transduction mechanisms of platelet endothelial cell adhesion molecule 1-vascular endothelial-cadherin-vascular endothelial growth factor receptor 2 complex,primary cilia,ion channels,and other mechanical sensors that affect some cardiac malformations.
Animals ; Heart/embryology* ; Humans ; Mechanotransduction, Cellular ; Myocytes, Cardiac/physiology* ; Vascular Endothelial Growth Factor A/metabolism*

Animals ; Cdc20 Proteins/metabolism* ; Cell Line ; Embryo, Mammalian/embryology* ; Embryonic Development ; Female ; Infertility, Female/metabolism* ; Mice ; Mutation ; Oocytes/metabolism*

Cloacal malformations are characterized by the confluence of the lower urinary tract, the female reproductive tract, and the rectum to create a common channel with a single opening on the perineum. The presence of a cloaca is a normal phase of early human embryological development. Between the 4^th and 7^th weeks of gestation, the cloaca undergoes subdivision to form the hindgut and urogenital sinus. Failure of this process results in the congenital anomaly termed persistent cloaca (PC). The term urorectal septum malformation sequence (URSMS) is also used to describe this anomaly. The classic description of this process which is still cited in many standard textbooks dates from the 19^th century. However, this has been increasingly called into question by the findings of studies using modern scientific methodology. Urogenital sinus anomalies are defined by the confluence of the urethra and vagina to form a common channel of varying length with a single perineal opening. In this condition, the anorectal canal opens separately on the perineum. The presence of a urogenital sinus represents a transient phase of the normal development of the lower genital tract in the female fetus. However, the form of urogenital sinus most commonly encountered in the developed world is a feature of disordered sexual differentiation and does not arise simply from the persistence of the anatomical structure which is a feature of normal fetal development.
Cloaca/embryology* ; Female ; Humans ; Urogenital Abnormalities/embryology* ; Vagina/embryology*

Understanding limb development not only gives insights into the outgrowth and differentiation of the limb, but also has clinical relevance. Limb development begins with two paired limb buds (forelimb and hindlimb buds), which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm, termed the apical ectodermal ridge (AER). As a transitional embryonic structure, the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres, feedback loops, and other cell activities by secretory signalling and the activation of gene expression. Within the scope of proximodistal patterning, it is understood that while fibroblast growth factors (FGFs) function sequentially over time as primary components of the AER signalling process, there is still no consensus on models that would explain proximodistal patterning itself. In anteroposterior patterning, the AER has a dual-direction regulation by which it promotes the sonic hedgehog (Shh) gene expression in the zone of polarizing activity (ZPA) for proliferation, and inhibits Shh expression in the anterior mesenchyme. In dorsoventral patterning, the AER activates Engrailed-1 (En1) expression, and thus represses Wnt family member 7a (Wnt7a) expression in the ventral ectoderm by the expression of Fgfs, Sp6/8, and bone morphogenetic protein (Bmp) genes. The AER also plays a vital role in shaping the individual digits, since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis. In summary, the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern formation, as the development of its areas proceeds simultaneously.
Animals ; Apoptosis ; Body Patterning ; Bone Morphogenetic Proteins/biosynthesis* ; Developmental Biology ; Ectoderm/metabolism* ; Extremities/embryology* ; Fibroblast Growth Factor 10/metabolism* ; Fibroblast Growth Factors/biosynthesis* ; Gene Expression Regulation ; Hedgehog Proteins/biosynthesis* ; Homeodomain Proteins/biosynthesis* ; Mesoderm/metabolism* ; Mice ; Signal Transduction ; Wnt Proteins/biosynthesis*

In their embryology, Aristotle and Galen greatly disagreed on the role of human derived materials like menstrual blood and vaginal secretion (called by them female sperm or semen). This gap made those two ancients also disagree on their understanding of mother's role in the generation of the human body in her womb. During the Middle Ages, especially during the thirteenth century, the scholastics drew on those two ancient thoughts for some rational underpinnings of their philosophical and theological doctrines. However, the manners of adoption and assimilation were varied. For example, Albert the Great strived to reconcile the two in the image of Avicenna, one of the main and the most important sources of Galenist medicine in the thirteenth Century. By contrast, those scholastics who played an important role in the controversy over plurality/unicity of the substantial form, drew on their disagreements. For example, pluralists like Bonaventure, William of la Mare, and Duns Scotus appealed to Galenist medical perspective to underpin their positions and paved ways to decorate Virgin Mary's motherhood and her active contribution to the Virgin birth and to the manhood of her Holy Son. in contrast a unicist like Thomas Aquinas advanced his theory in line with Aristotelian model that Mary's role in her Son's birth and manhood was passive and material. Giles, another unicist, while repudiating Galenist embryology with the support of Averroes's medical work called Colliget, alluded to some theologically crucial impieties with which might be associated some pluralists' Mariology based on the Roman physician's model. In this processus historiae, we can see not only the intertwining of medieval medicine, philosophy, and theology, but some critical moments where medicine provided, side by side with philosophy, natural settings and explanations for religious marvels or miracles such as the Virgin birth, the motherhood of Mary, the manhood of Christ, etc. Likewise, we can observe two medieval maxims coincide and resonate: “philosophia ancilla theologiae” and “philosophia et medicina duae sorores sunt.”
Embryology ; Female ; Human Body ; Humans ; Parturition ; Philosophy ; Spermatozoa ; Theology

PURPOSE: There are known differences in embryology, clinical symptoms, incidences, molecular pathways involved, and oncologic outcomes of right-sided and left-sided colorectal cancers. However, immunologic study has only been characterized for healthy adults. The present study was designed to identify differences in immune cell populations in patients with right-sided and left-sided colorectal cancers.METHODS: A total of 35 patients who underwent colorectal resection for cancer between November 2016 and August 2017 at a tertiary teaching hospital were enrolled in this study. Patients were excluded if they had a disease affecting their immune system. Populations of immune cells, including mucosal-associated invariant T (MAIT), gamma delta T, invariant natural killer T, T, natural killer, and B cells, were measured in the peripheral blood and cancer tissues using flow cytometry, and then assessed based on the origin of the colorectal cancer.RESULTS: Fifteen had right-side and 20 had left-side colorectal cancer. There were no significant differences between the 2 cohorts for patient characteristics including pathologic stage. Peripheral blood from patients with right-side colon cancers contained fewer MAIT (0.87% right-side vs. 1.74% left-side, P = 0.028) and gamma delta T cells (1.10% right-side vs. 3.05% left-side, P = 0.002). Although the group with right-side colorectal cancer had more MAIT cells in cancer tissues (1.71% vs. 1.00%), this difference was not statistically significant.CONCLUSION: There is a difference in population sizes of immune cells in blood between patients with right-sided and leftsided colon cancers. The immune cell composition was determined to be distinct based on embryologic origin.
Adult ; B-Lymphocytes ; Cohort Studies ; Colonic Neoplasms ; Colorectal Neoplasms ; Embryology ; Flow Cytometry ; Hospitals, Teaching ; Humans ; Immune System ; Incidence ; Population Density ; T-Lymphocytes

Light sheet microscopy (LSM) is an evolving optical imaging technique with a plane illumination for optical sectioning and volumetric imaging spanning cell biology, embryology, and in vivo live imaging. Here, we focus on emerging biomedical applications of LSM for tissue samples. Decoupling of the light sheet illumination from detection enables high-speed and large field-of-view imaging with minimal photobleaching and phototoxicity. These unique characteristics of the LSM technique can be easily adapted and potentially replace conventional histopathological procedures. In this review, we cover LSM technology from its inception to its most advanced technology; in particular, we highlight the human histopathological imaging applications to demonstrate LSM's rapid diagnostic ability in comparison with conventional histopathological procedures. We anticipate that the LSM technique can become a useful three-dimensional imaging tool for assessing human biopsies in the near future.
Biopsy ; Dermatitis, Phototoxic ; Embryology ; Humans ; Imaging, Three-Dimensional ; Lighting ; Microscopy ; Optical Imaging ; Photobleaching