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题目:: Synthetic lateral inhibition governs cell-type bifurcation with robust ratios.
作者:: Matsuda(Mitsuhiro),Koga(Makito),Woltjen(Knut),Nishida(Eisuke),Ebisuya(Miki)
状态:: 发布时间2015-02-05 , 更新时间 2015-02-05
期刊:: Nat Commun
摘要:: 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.
语言:: eng
DOI:: 10.1038/ncomms7195

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