84 research outputs found

    Shape Self-Regulation in Early Lung Morphogenesis

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    The arborescent architecture of mammalian conductive airways results from the repeated branching of lung endoderm into surrounding mesoderm. Subsequent lung’s striking geometrical features have long raised the question of developmental mechanisms involved in morphogenesis. Many molecular actors have been identified, and several studies demonstrated the central role of Fgf10 and Shh in growth and branching. However, the actual branching mechanism and the way branching events are organized at the organ scale to achieve a self-avoiding tree remain to be understood through a model compatible with evidenced signaling. In this paper we show that the mere diffusion of FGF10 from distal mesenchyme involves differential epithelial proliferation that spontaneously leads to branching. Modeling FGF10 diffusion from sub-mesothelial mesenchyme where Fgf10 is known to be expressed and computing epithelial and mesenchymal growth in a coupled manner, we found that the resulting laplacian dynamics precisely accounts for the patterning of FGF10-induced genes, and that it spontaneously involves differential proliferation leading to a self-avoiding and space-filling tree, through mechanisms that we detail. The tree’s fine morphological features depend on the epithelial growth response to FGF10, underlain by the lung’s complex regulatory network. Notably, our results suggest that no branching information has to be encoded and that no master routine is required to organize branching events at the organ scale. Despite its simplicity, this model identifies key mechanisms of lung development, from branching to organ-scale organization, and could prove relevant to the development of other branched organs relying on similar pathways

    Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

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    Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

    Distribution of neuronal cannabinoid receptor in the adult rat brain: A comparative receptor binding radioautography and in situ hybridization histochemistry

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    The neuronal distribution of cannabinoid receptor in the adult rat brain is reported, combining receptor binding radioautography using the synthetic psychoactive cannabinoid ligand CP55,940 with in situ hybridization histochemistry using oligonucleotide probes complementary to rat cannabinoid receptor cDNA. In the cerebral cortex, especially in the frontal and cingulate cortex, dense binding was found in layers I and VI together with slight mRNA levels in a majority of both pyramidal and non-pyramidal-shaped neurons and of high mRNA levels in a moderate number of non-pyramidal-shaped neurons especially in layers II-III and V-VI. In the hippocampal dentate gyrus, very dense staining was found in the molecular layer together with high mRNA levels in a moderate number of bilar neurons close to the granular layer. In Ammon's horn, especially in the CA3 sector, very dense binding was found in the dendritic layers together with slight mRNA levels in the majority of the pyramidal cells and high mRNA levels in a moderate number of interneurons. In the basal ganglia, binding was very dense n the lateral putamen, substantia nigra pars reticulata, globus pallidus and entopeduncular nucleus, moderate in the medial putamen and caudate; and slight in the accumbens, together with slight to moderate mRNA levels in the striatal medium-sized neurons. Together with slight binding, slight to moderate mRNA levels were found in the majority of the neurons in the subthalamic nucleus. No binding and mRNA were found in the substantia nigra pars compacta and ventral tegmental area. Slight to moderate binding was found together with slight to moderate mRNA levels in the majority of neurons in the anterior olfactory nucleus; septum, especially medial septum and diagonal band of Broca; amygdala, especially basolateral amygdala; lateral habenula; ventromedial hypothalamic nucleus; lateral interpeduncular nucleus; central gray, dorsal cochlear nucleus; parabrachial nucleus; dorsal pontine tegmentum; pontine nuclei; commissural part of the nucleus tractus solitarius; inferior olive and dorsal horn of the spinal cord. In the cerebellum, very dense binding was found in the molecular layer together with slight mRNA levels in the majority of the granule cells and moderate mRNA levels in the basket and stellate cells. In conclusion, this study provides, for the first time, indirect assessment of the neurons containing cannabinoid receptor in the entire adult rat brain and will serve as a basis for future direct morphological confirmation using receptor immunohistochemistry and for functional studies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Cholecystokinin receptors of A type in the human dorsal medulla oblongata and meningiomas, and of B type in small cell lung carcinomas

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    Cholecystokinin receptors of the pancreatic type (A type) were found in the infant and adult human area postrema, medial nucleus tractus solitarius, vagus dorsal motor nucleus and in the meningiomas, and of the brain type (B type) in the ventral nucleus tractus solitarius and in the small cell lung carcinomas.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Age-related loss of cannabinoid receptor binding sites and mRNA in the rat striatum

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    Differences in the distribution of cannabinoid receptor (studied by receptor binding radioautography using the synthetic psychoactive cannabinoid ligand [3H]CP55,940) and its mRNA (studied by in situ hybridization histochemistry using oligonucleotide probes complementary to rat cannabinoid receptor cDNA) have been investigated in the rat striatum during ageing. The striata of old rats (24 months) show a 50% reduction in expression of cannabinoid receptors and mRNA levels when compared with young (3 months) equivalents. Thus, changes in cannabinoid receptor gene expression appear to be partially responsible for age-related loss of these receptors.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Glutamatergic regulation of cannabinoid receptor gene expression in the caudate-putamen

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    Glutamatergic regulation of δ-9-tetrahydrocannabinol (THC) receptor gene expression in the adult rat dorsal striatum following a 2 week unilateral cerebral decortication or pharmacological treatment with MK-801 was investigated by quantitative in situ hybridization. The caudate-putamen on the side of the cerebral decortication contains about 30% significantly lower mRNA levels than the control. In addition, we observed a 52% significant decrease in THC receptor mRNA levels in intact dorsal striatum after treatment with MK-801. Together these results suggest that in vivo, through the NMDA receptor subtype, glutamate up-regulates THC receptor gene expression in the rat caudate-putamen.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons

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    In the infant and adult human basal ganglia, the finding of mRNA exclusively in the striatal medium-sized neurons together with the detection of [3H]CP55,940 binding sites in the caudate-putamen, accumbens, substantia nigra pars reticulata and globus pallidus suggests cannabinoid receptor localization on the striatal intrinsic enkephalinergic and substance P-projecting neurons and on their nigral and pallidal terminals. However, the consistent finding of higher binding in the substantia nigra pars reticulata and medial part of the globus pallidus over its lateral segment suggests cannabinoid receptor enrichment on the striatal substance P neurons which express selectively the dopamine D1 receptor. © 1992.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    delta-9-tetrahydrocannabinol regulates substance P and enkephalin mRNAs levels in the caudate-putamen

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    SCOPUS: ar.jinfo:eu-repo/semantics/publishe
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