Author
Listed:
- Mitsuhiro Matsuda
(RIKEN Center for Developmental Biology
Career-Path Promotion Unit for Young Life Scientists, Kyoto University
Graduate School of Biostudies, Kyoto University
Present address: Laboratory for Reconstitutive Developmental Biology, RIKEN Quantitative Biology Center, 2-2-3 Minatojima-minamimachi, Kobe, Hyogo 650-0047, Japan)
- Makito Koga
(RIKEN Center for Developmental Biology
Career-Path Promotion Unit for Young Life Scientists, Kyoto University
Graduate School of Biostudies, Kyoto University)
- Knut Woltjen
(Center for iPS Cell Research and Application, Kyoto University
Hakubi Center for Advanced Research, Kyoto University)
- Eisuke Nishida
(Graduate School of Biostudies, Kyoto University)
- Miki Ebisuya
(RIKEN Center for Developmental Biology
Career-Path Promotion Unit for Young Life Scientists, Kyoto University
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST)
Present address: Laboratory for Reconstitutive Developmental Biology, RIKEN Quantitative Biology Center, 2-2-3 Minatojima-minamimachi, Kobe, Hyogo 650-0047, 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.
Suggested Citation
Mitsuhiro Matsuda & Makito Koga & Knut Woltjen & Eisuke Nishida & Miki Ebisuya, 2015.
"Synthetic lateral inhibition governs cell-type bifurcation with robust ratios,"
Nature Communications, Nature, vol. 6(1), pages 1-12, May.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7195
DOI: 10.1038/ncomms7195
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