@article{7202, abstract = {The cerebral cortex contains multiple areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modelling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas.}, author = {Llorca, Alfredo and Ciceri, Gabriele and Beattie, Robert J and Wong, Fong Kuan and Diana, Giovanni and Serafeimidou-Pouliou, Eleni and Fernández-Otero, Marian and Streicher, Carmen and Arnold, Sebastian J. and Meyer, Martin and Hippenmeyer, Simon and Maravall, Miguel and Marín, Oscar}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture}}, doi = {10.7554/eLife.51381}, volume = {8}, year = {2019}, } @article{6451, abstract = {Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis inmice and humans, and its deficiency causes severe skin inflammation, which might affect epidermalstem cell behavior. Here, we describe the inflammation-independent effects of EGFR deficiency dur-ing skin morphogenesis and in adult hair follicle stem cells. Expression and alternative splicing analysisof RNA sequencing data from interfollicular epidermis and outer root sheath indicate that EGFR con-trols genes involved in epidermal differentiation and also in centrosome function, DNA damage, cellcycle, and apoptosis. Genetic experiments employingp53deletion in EGFR-deficient epidermis revealthat EGFR signaling exhibitsp53-dependent functions in proliferative epidermal compartments, aswell asp53-independent functions in differentiated hair shaft keratinocytes. Loss of EGFR leads toabsence of LEF1 protein specifically in the innermost epithelial hair layers, resulting in disorganizationof medulla cells. Thus, our results uncover important spatial and temporal features of cell-autonomousEGFR functions in the epidermis.}, author = {Amberg, Nicole and Sotiropoulou, Panagiota A. and Heller, Gerwin and Lichtenberger, Beate M. and Holcmann, Martin and Camurdanoglu, Bahar and Baykuscheva-Gentscheva, Temenuschka and Blanpain, Cedric and Sibilia, Maria}, issn = {2589-0042}, journal = {iScience}, pages = {243--256}, publisher = {Elsevier}, title = {{EGFR controls hair shaft differentiation in a p53-independent manner}}, doi = {10.1016/j.isci.2019.04.018}, volume = {15}, year = {2019}, } @article{27, abstract = {The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell-type diversity during cortical development. This article is protected by copyright. All rights reserved.}, author = {Amberg, Nicole and Laukoter, Susanne and Hippenmeyer, Simon}, journal = {Journal of Neurochemistry}, number = {1}, pages = {12--26}, publisher = {Wiley}, title = {{Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex}}, doi = {10.1111/jnc.14601}, volume = {149}, year = {2019}, } @article{7399, abstract = {Long non-coding (lnc) RNAs are numerous and found throughout the mammalian genome, and many are thought to be involved in the regulation of gene expression. However, the majority remain relatively uncharacterised and of uncertain function making the use of model systems to uncover their mode of action valuable. Imprinted lncRNAs target and recruit epigenetic silencing factors to a cluster of imprinted genes on the same chromosome, making them one of the best characterized lncRNAs for silencing distant genes in cis. In this study we examined silencing of the distant imprinted gene Slc22a3 by the lncRNA Airn in the Igf2r imprinted cluster in mouse. Previously we proposed that imprinted lncRNAs may silence distant imprinted genes by disrupting promoter-enhancer interactions by being transcribed through the enhancer, which we called the enhancer interference hypothesis. Here we tested this hypothesis by first using allele-specific chromosome conformation capture (3C) to detect interactions between the Slc22a3 promoter and the locus of the Airn lncRNA that silences it on the paternal chromosome. In agreement with the model, we found interactions enriched on the maternal allele across the entire Airn gene consistent with multiple enhancer-promoter interactions. Therefore, to test the enhancer interference hypothesis we devised an approach to delete the entire Airn gene. However, the deletion showed that there are no essential enhancers for Slc22a2, Pde10a and Slc22a3 within the Airn gene, strongly indicating that the Airn RNA rather than its transcription is responsible for silencing distant imprinted genes. Furthermore, we found that silent imprinted genes were covered with large blocks of H3K27me3 on the repressed paternal allele. Therefore we propose an alternative hypothesis whereby the chromosome interactions may initially guide the lncRNA to target imprinted promoters and recruit repressive chromatin, and that these interactions are lost once silencing is established.}, author = {Andergassen, Daniel and Muckenhuber, Markus and Bammer, Philipp C. and Kulinski, Tomasz M. and Theussl, Hans-Christian and Shimizu, Takahiko and Penninger, Josef M. and Pauler, Florian and Hudson, Quanah J.}, issn = {1553-7404}, journal = {PLoS Genetics}, number = {7}, publisher = {Public Library of Science}, title = {{The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes}}, doi = {10.1371/journal.pgen.1008268}, volume = {15}, year = {2019}, } @article{6830, author = {Contreras, Ximena and Hippenmeyer, Simon}, issn = {10974199}, journal = {Neuron}, number = {5}, pages = {750--752}, publisher = {Elsevier}, title = {{Memo1 tiles the radial glial cell grid}}, doi = {10.1016/j.neuron.2019.08.021}, volume = {103}, year = {2019}, }