RT Journal Article
SR Electronic
T1 Feedback control of neurogenesis by tissue packing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 252445
DO 10.1101/252445
A1 Hiscock, Tom W.
A1 Miesfeld, Joel B.
A1 Mosaliganti, Kishore R.
A1 Link, Brian A.
A1 Megason, Sean G.
YR 2018
UL http://biorxiv.org/content/early/2018/01/23/252445.abstract
AB 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.