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Nat Commun. 2015 Feb 5;6:6195. doi: 10.1038/ncomms7195.

Synthetic lateral inhibition governs cell-type bifurcation with robust ratios.

Author information

1
1] RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto 606-8501, Japan [3] Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
2
1] Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan [2] Hakubi Center for Advanced Research, Kyoto University, Kyoto 606-8501, Japan.
3
Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
4
1] RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto 606-8501, Japan [3] Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.

Abstract

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.

PMID:
25652697
DOI:
10.1038/ncomms7195
[Indexed for MEDLINE]

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