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Signaling-dependent control of apical membrane size and self-renewal in rosette-stage human neuroepithelial stem cells

Jan-Philip Medelnik, Kathleen Roensch, Satoshi Okawa, Antonio del Sol, Osvaldo Chara, Levan Mchedlishvili, Elly M. Tanaka
doi: https://doi.org/10.1101/222125
Jan-Philip Medelnik
1DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany
2Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany
6Research Institute for Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, 1030,Vienna, Austria, (Current address)
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  • For correspondence: jan.medelnik@imp.ac.at
Kathleen Roensch
1DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany
2Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany
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Satoshi Okawa
5Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6, Avenue du Swing,Belvaux L-4367, Luxembourg
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Antonio del Sol
5Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6, Avenue du Swing,Belvaux L-4367, Luxembourg
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Osvaldo Chara
3Center for Information Services and High Performance Computing (ZIH), Technische Universität Dresden, 01062 Dresden, Germany
4Systems Biology Group (SysBio), Instituto de Fisica de Líquidos y Sistemas Biologicos (IFLySIB), CONICET, Universidad Nacional de LaPlata (UNLP), B1900BTE La Plata, Buenos Aires, Argentina
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Levan Mchedlishvili
1DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany
2Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany
7current address: University Hospital Greifswald Department of Neurosurgery, Sauerbruchstraße 17475, Greifswald
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Elly M. Tanaka
1DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden, Germany
2Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany
6Research Institute for Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, 1030,Vienna, Austria, (Current address)
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Summary

In the early developing nervous system, self-renewing neural stem cells are polarized and maintain an apical domain facing a central lumen. The presence of apical membrane is thought to have a profound influence on maintaining the stem cell state. With the onset of neurogenesis cells lose their polarization and the concomitant loss of the apical domain coincides with a loss of the stem cell identity. Very little is known about the molecular signals controlling apical membrane size. Here we use two neuroepithelial cell systems, one derived from regenerating axolotl spinal cord and the other from human ESCs to identify a conserved molecular signalling pathway initiated by lysophosphatidic acid (LPA) that controls apical membrane size and consequently controls and maintains epithelial organization and lumen size in neuroepithelial rosettes. This apical domain size increase occurs independently of effects on proliferation and involves a SRF-dependent transcriptional induction of junctional and apical membrane components.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 23, 2017.
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Signaling-dependent control of apical membrane size and self-renewal in rosette-stage human neuroepithelial stem cells
Jan-Philip Medelnik, Kathleen Roensch, Satoshi Okawa, Antonio del Sol, Osvaldo Chara, Levan Mchedlishvili, Elly M. Tanaka
bioRxiv 222125; doi: https://doi.org/10.1101/222125
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Signaling-dependent control of apical membrane size and self-renewal in rosette-stage human neuroepithelial stem cells
Jan-Philip Medelnik, Kathleen Roensch, Satoshi Okawa, Antonio del Sol, Osvaldo Chara, Levan Mchedlishvili, Elly M. Tanaka
bioRxiv 222125; doi: https://doi.org/10.1101/222125

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