論文

査読有り
2015年2月

Synthetic lateral inhibition governs cell-type bifurcation with robust ratios

NATURE COMMUNICATIONS
  • Mitsuhiro Matsuda
  • ,
  • Makito Koga
  • ,
  • Knut Woltjen
  • ,
  • Eisuke Nishida
  • ,
  • Miki Ebisuya

6
6195
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/ncomms7195
出版者・発行元
NATURE PUBLISHING GROUP

Cell-type diversity in multicellular organisms is created through a series of binary cell fate decisions. Lateral inhibition controlled by Delta-Notch signalling is the core mechanism for the choice of alternative cell types by homogeneous neighbouring cells. Here, we show that cells engineered with a Delta-Notch-dependent lateral inhibition circuit spontaneously bifurcate into Delta-positive and Notch-active cell populations. The synthetic lateral inhibition circuit comprises transcriptional repression of Delta and intracellular feedback of Lunatic fringe (Lfng). The Lfng-feedback subcircuit, even alone, causes the autonomous cell-type bifurcation. Furthermore, the ratio of two cell populations bifurcated by lateral inhibition is reproducible and robust against perturbation. The cell-type ratio is adjustable by the architecture of the lateral inhibition circuit as well as the degree of cell-cell attachment. Thus, the minimum lateral inhibition mechanism between adjacent cells not only serves as a binary cell-type switch of individual cells but also governs the cell-type ratio at the cell-population level.

リンク情報
DOI
https://doi.org/10.1038/ncomms7195
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000350201100004&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/ncomms7195
  • ISSN : 2041-1723
  • Web of Science ID : WOS:000350201100004

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