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Feedback control of neurogenesis by tissue packing

View ORCID ProfileTom W. Hiscock, Joel B. Miesfeld, Kishore R. Mosaliganti, Brian A. Link, Sean G. Megason
doi: https://doi.org/10.1101/252445
Tom W. Hiscock
1Department of Systems Biology, Harvard Medical School, Boston, MA, 02115.
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Joel B. Miesfeld
2Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
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Kishore R. Mosaliganti
1Department of Systems Biology, Harvard Medical School, Boston, MA, 02115.
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Brian A. Link
2Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
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Sean G. Megason
1Department of Systems Biology, Harvard Medical School, Boston, MA, 02115.
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Abstract

Balancing the rate of differentiation and proliferation in developing tissues is essential to produce organs of robust size and composition. Whilst many molecular regulators have been established, how these connect to physical and geometrical aspects of tissue architecture is poorly understood. Here, using high-resolution timelapse imaging, we find that dense tissue packing and complex cell geometries play a significant role in regulating differentiation rate in the zebrafish neural tube. Specifically, in regions of high cell density, progenitors are physically pushed away from the apical surface, which, in a Notch-dependent manner, leads to their differentiation. Using simulations we show that this naturally performs negative feedback control on cell number. Our results suggest a model whereby differentiation rate is carefully tuned to correct fluctuations in cell number, originating from variable cell cycle progression and inherently probabilistic differentiation programs.

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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 January 23, 2018.
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Feedback control of neurogenesis by tissue packing
Tom W. Hiscock, Joel B. Miesfeld, Kishore R. Mosaliganti, Brian A. Link, Sean G. Megason
bioRxiv 252445; doi: https://doi.org/10.1101/252445
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Feedback control of neurogenesis by tissue packing
Tom W. Hiscock, Joel B. Miesfeld, Kishore R. Mosaliganti, Brian A. Link, Sean G. Megason
bioRxiv 252445; doi: https://doi.org/10.1101/252445

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