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Experimental Cell Research Oct 2023Primary cilia are non-motile, microtubule-based sensory organelle present in most vertebrate cells with a fundamental role in the modulation of organismal development,... (Review)
Review
Primary cilia are non-motile, microtubule-based sensory organelle present in most vertebrate cells with a fundamental role in the modulation of organismal development, morphogenesis, and repair. Here we focus on the role of primary cilia in embryonic and postnatal skeletal development. We examine evidence supporting its involvement in physiochemical and developmental signaling that regulates proliferation, patterning, differentiation and homeostasis of osteoblasts, chondrocytes, and their progenitor cells in the skeleton. We discuss how signaling effectors in mechanotransduction and bone development, such as Hedgehog, Wnt, Fibroblast growth factor and second messenger pathways operate at least in part at the primary cilium. The relevance of primary cilia in bone formation and maintenance is underscored by a growing list of rare genetic skeletal ciliopathies. We collate these findings and summarize the current understanding of molecular factors and mechanisms governing primary ciliogenesis and ciliary function in skeletal development and disease.
Topics: Cilia; Humans; Animals; Bone and Bones; Skeleton; Organogenesis; Osteogenesis; Signal Transduction; Mechanotransduction, Cellular
PubMed: 37574037
DOI: 10.1016/j.yexcr.2023.113751 -
Obstetrics and Gynecology Sep 2023The distinction between “pregnancy viability” and “fetal viability” indicates the need for care and clarity when using the term “viability” in clinical...
The distinction between “pregnancy viability” and “fetal viability” indicates the need for care and clarity when using the term “viability” in clinical practice and guidance.
Topics: Humans; Gestational Age; Fetal Viability
PubMed: 37535950
DOI: 10.1097/AOG.0000000000005280 -
Nature Methods Nov 2023
Topics: Models, Biological; Morphogenesis
PubMed: 37935984
DOI: 10.1038/s41592-023-02075-8 -
Advances in Experimental Medicine and... 2024Some members of the Firmicutes phylum, including many members of the human gut microbiota, are able to differentiate a dormant and highly resistant cell type, the... (Review)
Review
Some members of the Firmicutes phylum, including many members of the human gut microbiota, are able to differentiate a dormant and highly resistant cell type, the endospore (hereinafter spore for simplicity). Spore-formers can colonize virtually any habitat and, because of their resistance to a wide variety of physical and chemical insults, spores can remain viable in the environment for long periods of time. In the anaerobic enteric pathogen Clostridioides difficile the aetiologic agent is the oxygen-resistant spore, while the toxins produced by actively growing cells are the main cause of the disease symptoms. Here, we review the regulatory circuits that govern entry into sporulation. We also cover the role of spores in the infectious cycle of C. difficile in relation to spore structure and function and the main control points along spore morphogenesis.
Topics: Humans; Clostridioides difficile; Gastrointestinal Microbiome; Morphogenesis; Oxygen; Physical Examination
PubMed: 38175480
DOI: 10.1007/978-3-031-42108-2_13 -
Cellular and Molecular Life Sciences :... Jul 2023Kindlin-2 is critical for development and homeostasis of key organs, including skeleton, liver, islet, etc., yet its role in modulating angiogenesis is unknown. Here, we...
Kindlin-2 is critical for development and homeostasis of key organs, including skeleton, liver, islet, etc., yet its role in modulating angiogenesis is unknown. Here, we report that sufficient KINDLIN-2 is extremely important for NOTCH-mediated physiological angiogenesis. The expression of KINDLIN-2 in HUVECs is significantly modulated by angiogenic factors such as vascular endothelial growth factor A or tumor necrosis factor α. A strong co-localization of CD31 and Kindlin-2 in tissue sections is demonstrated by immunofluorescence staining. Endothelial-cell-specific Kindlin-2 deletion embryos die on E10.5 due to hemorrhage caused by the impaired physiological angiogenesis. Experiments in vitro show that vascular endothelial growth factor A-induced multiple functions of endothelial cells, including migration, matrix proteolysis, morphogenesis and sprouting, are all strengthened by KINDLIN-2 overexpression and severely impaired in the absence of KINDLIN-2. Mechanistically, we demonstrate that KINDLIN-2 inhibits the release of Notch intracellular domain through binding to and maintaining the integrity of NOTCH1. The impaired angiogenesis and avascular retinas caused by KINDLIN-2 deficiency can be rescued by DAPT, an inhibitor of γ-secretase which releases the intracellular domain from NOTCH1. Moreover, we demonstrate that high glucose stimulated hyperactive angiogenesis by increasing KINDLIN-2 expression could be prevented by KINDLIN-2 knockdown, indicating Kindlin-2 as a potential therapeutic target in treatment of diabetic retinopathy. Our study for the first time demonstrates the significance of Kindlin-2 in determining Notch-mediated angiogenesis during development and highlights Kindlin-2 as the potential therapeutic target in angiogenic diseases, such as diabetic retinopathy.
Topics: Humans; Cardiovascular Physiological Phenomena; Diabetic Retinopathy; Endothelial Cells; Morphogenesis; Vascular Endothelial Growth Factor A
PubMed: 37480504
DOI: 10.1007/s00018-023-04866-w -
Neuroscience Aug 2023Although hypoxic postconditioning (HPC) has a protective effect on ischemic stroke, its effect on angiogenesis after ischemic stroke is still unclear. This study was...
Although hypoxic postconditioning (HPC) has a protective effect on ischemic stroke, its effect on angiogenesis after ischemic stroke is still unclear. This study was designed to investigate the effects of HPC on angiogenesis after ischemic stroke and to preliminarily study the mechanism involved. Oxygen-glucose deprivation (OGD)-intervened bEnd.3 (mouse brain-derived Endothelial cell. 3) was used to simulate cerebral ischemia. Cell counting kit-8 (CCK-8), Cell BrdU proliferation, wound healing, Transwell and tube formation assays were used to evaluate the effect of HPC on the cell viability, proliferation, migration (horizontal and vertical migration), morphogenesis and tube formation of bEnd.3. A middle cerebral artery occlusion (MCAO) model was made in C57 mice to simulate focal cerebral ischemia. Rod rotation test, corner test, modified neurological severity score (mNSS), and balance beam walking test were used to evaluate the effect of HPC on the neurological impairment of mice. Immunofluorescence staining was used to evaluate the effect of HPC on angiogenesis in mice. The angiogenesis-related proteins were evaluated and quantified using western blot. Results showed that HPC significantly promoted proliferation, migration and tube formation of bEnd.3. HPC significantly reversed the neurological deficit of MCAO mice. Moreover, HPC significantly promoted angiogenesis in the peri-infarct area, and angiogenesis was found to be positively correlated with the improvement of neurological impairment. The HPC mice showed higher PLCλ and ALK5 than did MCAO. We conclude that HPC improves the neurological deficit caused by focal cerebral ischemia by promoting angiogenesis. Furthermore, the effect of HPC on improving angiogenesis may be related to PLCλ and ALK5.
Topics: Mice; Animals; Ischemic Stroke; Brain Ischemia; Infarction, Middle Cerebral Artery; Morphogenesis; Stroke; Ischemic Postconditioning
PubMed: 37331689
DOI: 10.1016/j.neuroscience.2023.06.009 -
Annual Review of Vision Science Sep 2023Proper eye structure is essential for visual function: Multiple essential eye tissues must take shape and assemble into a precise three-dimensional configuration.... (Review)
Review
Proper eye structure is essential for visual function: Multiple essential eye tissues must take shape and assemble into a precise three-dimensional configuration. Accordingly, alterations to eye structure can lead to pathological conditions of visual impairment. Changes in eye shape can also be adaptive over evolutionary time. Eye structure is first established during development with the formation of the optic cup, which contains the neural retina, retinal pigment epithelium, and lens. This crucial yet deceptively simple hemispherical structure lays the foundation for all later elaborations of the eye. Building on descriptions of the embryonic eye that started with hand drawings and micrographs, the field is beginning to identify mechanisms driving dynamic changes in three-dimensional cell and tissue shape. A combination of molecular genetics, imaging, and pharmacological approaches is defining connections among transcription factors, signaling pathways, and the intracellular machinery governing the emergence of this crucial structure.
Topics: Animals; Vertebrates; Retina; Retinal Pigment Epithelium; Vision, Low; Morphogenesis
PubMed: 37040791
DOI: 10.1146/annurev-vision-100720-111125 -
Emerging Topics in Life Sciences Dec 2023Neurulation is a critical step in early embryonic development, giving rise to the neural tube, the primordium of the central nervous system in amniotes. Understanding... (Review)
Review
Neurulation is a critical step in early embryonic development, giving rise to the neural tube, the primordium of the central nervous system in amniotes. Understanding this complex, multi-scale, multi-tissue morphogenetic process is essential to provide insights into normal development and the etiology of neural tube defects. Innovations in tissue engineering have fostered the generation of pluripotent stem cell-based in vitro models, including organoids, that are emerging as unique tools for delving into neurulation mechanisms, especially in the context of human development. Each model captures specific aspects of neural tube morphogenesis, from epithelialization to neural tissue elongation, folding and cavitation. In particular, the recent models of human and mouse trunk morphogenesis, such as gastruloids, that form a spinal neural plate-like or neural tube-like structure are opening new avenues to study normal and pathological neurulation. Here, we review the morphogenetic events generating the neural tube in the mammalian embryo and questions that remain unanswered. We discuss the advantages and limitations of existing in vitro models of neurulation and possible future technical developments.
Topics: Mice; Animals; Humans; Neurulation; Neural Tube; Neural Tube Defects; Neural Plate; Stem Cells; Mammals
PubMed: 38087891
DOI: 10.1042/ETLS20230087 -
Integrative and Comparative Biology Dec 2023While the modern framework of evolutionary development (evo-devo) has been decidedly genetic, historic analyses have also considered the importance of mechanics in the... (Review)
Review
While the modern framework of evolutionary development (evo-devo) has been decidedly genetic, historic analyses have also considered the importance of mechanics in the evolution of form. With the aid of recent technological advancements in both quantifying and perturbing changes in the molecular and mechanical effectors of organismal shape, how molecular and genetic cues regulate the biophysical aspects of morphogenesis is becoming increasingly well studied. As a result, this is an opportune time to consider how the tissue-scale mechanics that underlie morphogenesis are acted upon through evolution to establish morphological diversity. Such a focus will enable a field of evo-devo mechanobiology that will serve to better elucidate the opaque relations between genes and forms by articulating intermediary physical mechanisms. Here, we review how the evolution of shape is measured and related to genetics, how recent strides have been made in the dissection of developmental tissue mechanics, and how we expect these areas to coalesce in evo-devo studies in the future.
Topics: Animals; Biological Evolution; Developmental Biology; Morphogenesis
PubMed: 37193661
DOI: 10.1093/icb/icad033 -
Cells Dec 2023The Hedgehog (Hh) pathway plays a crucial role in embryonic development, acting both as a morphogenic signal that organizes tissue formation and a potent mitogenic... (Review)
Review
The Hedgehog (Hh) pathway plays a crucial role in embryonic development, acting both as a morphogenic signal that organizes tissue formation and a potent mitogenic signal driving cell proliferation. Dysregulated Hh signaling leads to various developmental defects in the brain. This article aims to review the roles of Hh signaling in the development of the neocortex in the mammalian brain, focusing on its regulation of neural progenitor proliferation and neuronal production. The review will summarize studies on genetic mouse models that have targeted different components of the Hh pathway, such as the ligand Shh, the receptor Ptch1, the GPCR-like transducer Smo, the intracellular transducer Sufu, and the three Gli transcription factors. As key insights into the Hh signaling transduction mechanism were obtained from mouse models displaying neural tube defects, this review will also cover some studies on Hh signaling in neural tube development. The results from these genetic mouse models suggest an intriguing hypothesis that elevated Hh signaling may play a role in the gyrification of the brain in certain species. Additionally, the distinctive production of GABAergic interneurons in the dorsal cortex in the human brain may also be linked to the extension of Hh signaling from the ventral to the dorsal brain region. Overall, these results suggest key roles of Hh signaling as both a morphogenic and mitogenic signal during the forebrain development and imply the potential involvement of Hh signaling in the evolutionary expansion of the neocortex.
Topics: Female; Pregnancy; Humans; Animals; Mice; Hedgehog Proteins; Embryonic Development; Morphogenesis; Biological Evolution; Neocortex; Mammals
PubMed: 38201225
DOI: 10.3390/cells13010021