To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.
- MeSH
- analýza jednotlivých buněk MeSH
- buňky klasifikace MeSH
- lidé MeSH
- neokortex cytologie MeSH
- neuroglie klasifikace MeSH
- neurony klasifikace MeSH
- terminologie jako téma MeSH
- transkriptom * MeSH
- výpočetní biologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Generation of neurons in the embryonic neocortex is a balanced process of proliferation and differentiation of neuronal progenitor cells. Canonical Wnt signalling is crucial for expansion of radial glial cells in the ventricular zone and for differentiation of intermediate progenitors in the subventricular zone. We detected abundant expression of two transcrtiption factors mediating canonical Wnt signalling, Tcf7L1 and Tcf7L2, in the ventricular zone of the embryonic neocortex. Conditional knock-out analysis showed that Tcf7L2, but not Tcf7L1, is the principal Wnt mediator important for maintenance of progenitor cell identity in the ventricular zone. In the absence of Tcf7L2, the Wnt activity is reduced, ventricular zone markers Pax6 and Sox2 are downregulated and the neuroepithelial structure is severed due to the loss of apical adherens junctions. This results in decreased proliferation of radial glial cells, the reduced number of intermediate progenitors in the subventricular zone and hypoplastic forebrain. Our data show that canonical Wnt signalling, which is essential for determining the neuroepithelial character of the neocortical ventricular zone, is mediated by Tcf7L2.
- MeSH
- buněčná diferenciace genetika MeSH
- chlorid-hydrogenuhličitanové antiportéry MeSH
- down regulace genetika MeSH
- embryo savčí MeSH
- hipokampus cytologie embryologie MeSH
- mutace genetika MeSH
- myši transgenní MeSH
- myši MeSH
- neokortex cytologie embryologie MeSH
- nervové kmenové buňky fyziologie MeSH
- neurogeneze fyziologie MeSH
- neuroglie MeSH
- neurony fyziologie MeSH
- počet buněk MeSH
- proliferace buněk genetika MeSH
- protein 2 podobný transkripčnímu faktoru 7 genetika metabolismus MeSH
- proteiny T-boxu metabolismus MeSH
- proteiny Wnt metabolismus MeSH
- retinální gangliové buňky fyziologie MeSH
- signální transdukce genetika MeSH
- transkripční faktory SOXB1 metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In the mammalian neocortex, the calcium-binding protein calretinin is expressed in a subset of cortical interneurons. In the recent years, research on interneurons is one of the most rapidly growing fields in neuroscience. This review summarizes the actual knowledge of the functions of calretinin in neuronal homeostasis and particularly of the distribution, connectivity and physiological properties of calretinin expressing interneurons in the neocortex of rodents and primates, including humans. The possible neuroprotective role of calretinin and the presumed “resistance” of calretinin-expressing interneurons to various pathological processes are also discussed.
- MeSH
- financování organizované MeSH
- homeostáza fyziologie MeSH
- lidé MeSH
- neokortex cytologie fyziologie MeSH
- neurony fyziologie MeSH
- S100 kalcium vázající protein G fyziologie MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
The neocortex contains two neuron types, excitatory (glutamatergic) pyramidal cells and inhibitory nonpyramidal (GABAergic) cells. GABAergic, inhibitory interneurons are morphologically distinct from excitatory pyramidal cells and account for 20-25 % of all neocortical neurons. Recent studies discovered that besides morphological features, inhibitory interneurons are molecularly and physiologically heterogenous and differ significantly in arrangement and terminations of their axonal endings. In neocortical interneurons, GABA is also co-localized with calcium-binding proteins (parvalbumin, calbindin, calretinin), with neuropeptides and nitric oxide synthase. Axons of GABAergic neurons target distinct domains of pyramidal neurons. Double-bouquet, Martinotti and neurogliaform cells (CB-IR, CR-IR) target distal dendrites of pyramidal neurons and probably regulate the vertical integration of synaptic input along the dendritic tree of pyramids. Basket cells (PV-IR) innervate soma and proximal dendrites, and Chandelier cells (PV-IR) exhibit synaptic contacts on the axon initial segment of pyramidal neurons. GABAergic neocortical interneurons are interconnected by gap junctions. Most often coupling is bidirectional and occurs between interneurons of the same type. Cortical pyramidal neurons derive from the dorsal telencephalon while the majority of interneurons derive from the ganglionic eminences of the ventral telencephalon, and tangentially migrate into cortex. Adult mammalian neurogenesis is not restricted to the hippocampus, but a small number of the new neurons is also generated in the neocortex. New cortical neurons are GABAergic and co-express calbindin and calretinin. Quantitative analysis of selected areas of the neocortex (neuropsychiatric diseases, models of epilepsy, aging) demonstrate a decrease in density of PV-IR and CB-IR neurons but not CR-IR neurons.
- MeSH
- biologické modely MeSH
- financování organizované MeSH
- GABA metabolismus MeSH
- interneurony cytologie metabolismus MeSH
- lidé MeSH
- neokortex cytologie metabolismus MeSH
- neurony cytologie metabolismus MeSH
- pyramidové buňky cytologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
