Molecular and cellular regulation of neurogenic cell division: A link between apical cytokinesis and adherens junction complex

In embryonic neocortex, neurogenic mitoses are confined to the ventricular zone (VZ) surface and subventricular zone (SVZ). The points of cellular abscission for VZ divisions are immediately adjacent to the adherens junctions at the apical membrane. The mechanisms that couple neurogenic cell abscissions to this apical surface are not known. Citron kinase (CITK), a protein essential to neurogenic cell division, polarizes to the apical membrane in metaphase prior to ingression of the cleavage furrow and becomes confined to midbodies at the VZ surface during cellular abscission. I report that CITK interacts with two proteins, RanGTPase binding protein 9 (RanBPM) and Discs large 5 (Dlg5), which both localize to the adherens junctions. RNAi of RanBPM in vivo decreases the number of midbodies localized to the VZ surface and causes accumulation of cells in M-phase. Dlg5 mutation in mice causes disrupted CITK polarization and decreased M-phase cells at the apical surface of the VZ. Taken together, I conclude that interactions between CITK and RanBPM, and CITK and Dlg5 contribute to progression of events during apical neurogenic cell division. These data provide evidence for a direct molecular and functional link between the midbody and adherens junctional complex.

S‐phase duration is the main target of cell cycle regulation in neural progenitors of developing ferret neocortex

ABSTRACT The evolutionary expansion of the neocortex primarily reflects increases in abundance and proliferative capacity of cortical progenitors and in the length of the neurogenic period during development. Cell cycle parameters of neocortical progenitors are an important determinant of cortical development. The ferret (Mustela putorius furo), a gyrencephalic mammal, has gained increasing importance as a model for studying corticogenesis. Here, we have studied the abundance, proliferation, and cell cycle parameters of different neural progenitor types, defined by their differential expression of the transcription factors Pax6 and Tbr2, in the various germinal zones of developing ferret neocortex. We focused our analyses on postnatal day 1, a late stage of cortical neurogenesis when upper‐layer neurons are produced. Based on cumulative 5‐ethynyl‐2′‐deoxyuridine (EdU) labeling as well as Ki67 and proliferating cell nuclear antigen (PCNA) immunofluorescence, we determined the duration of the various cell cycle phases of the different neocortical progenitor subpopulations. Ferret neocortical progenitors were found to exhibit longer cell cycles than those of rodents and little variation in the duration of G1 among distinct progenitor types, also in contrast to rodents. Remarkably, the main difference in cell cycle parameters among the various progenitor types was the duration of S‐phase, which became shorter as progenitors progressively changed transcription factor expression from patterns characteristic of self‐renewal to those of neuron production. Hence, S‐phase duration emerges as major target of cell cycle regulation in cortical progenitors of this gyrencephalic mammal. J. Comp. Neurol. 524:456–470, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc

A community-based transcriptomics classification and nomenclature of neocortical cell types

© 2020, The Author(s). 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

Publisher Correction: A community-based transcriptomics classification and nomenclature of neocortical cell types (Nature Neuroscience, (2020), 23, 12, (1456-1468), 10.1038/s41593-020-0685-8)

© 2020, The Author(s). In the version of this article initially published, author Thomas V. Wuttke’s affiliation was shown incorrectly. Dr. Wuttke is affiliated with University of Tübingen, Tübingen, Germany. The error has been corrected in the PDF and HTML versions of this article

Publisher Correction: A community-based transcriptomics classification and nomenclature of neocortical cell types

In the version of this article initially published, author Thomas V. Wuttke’s affiliation was shown incorrectly. Dr. Wuttke is affiliated with University of Tübingen, Tübingen, Germany. The error has been corrected in the PDF and HTML versions of this article

A community-based transcriptomics classification and nomenclature of neocortical cell types

To understand the function of cortical circuits it is necessary to classify their underlying cellular diversity. Traditional attempts based on comparing anatomical or physiological features of neurons and glia, while productive, have not resulted in a unified taxonomy of neural cell types. The recent development of single-cell transcriptomics has enabled, for the first time, systematic high-throughput profiling of large numbers of cortical cells and the generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data have revealed the existence of clear clusters, many of which correspond to cell types defined by traditional criteria, and which are conserved across cortical areas and species. To capitalize on these innovations and advance the field, we, the Copenhagen Convention Group, propose the community adopts a transcriptome-based taxonomy of the cell types in the adult mammalian neocortex. This core classification should be ontological, hierarchical and use a standardized nomenclature. It should be configured to flexibly incorporate new data from multiple approaches, developmental stages and a growing number of species, enabling improvement and revision of the classification. This community-based strategy could serve as a common foundation for future detailed analysis and reverse engineering of cortical circuits and serve as an example for cell type classification in other parts of the nervous system and other organs