Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell. 2013 Apr 25;153(3):550-61. doi: 10.1016/j.cell.2013.03.023.
Sharply delineated domains of cell types arise in developing tissues under instruction of inductive signal (morphogen) gradients, which specify distinct cell fates at different signal levels. The translation of a morphogen gradient into discrete spatial domains relies on precise signal responses at stable cell positions. However, cells in developing tissues undergoing morphogenesis and proliferation often experience complex movements, which may affect their morphogen exposure, specification, and positioning. How is a clear pattern achieved with cells moving around? Using in toto imaging of the zebrafish neural tube, we analyzed specification patterns and movement trajectories of neural progenitors. We found that specified progenitors of different fates are spatially mixed following heterogeneous Sonic Hedgehog signaling responses. Cell sorting then rearranges them into sharply bordered domains. Ectopically induced motor neuron progenitors also robustly sort to correct locations. Our results reveal that cell sorting acts to correct imprecision of spatial patterning by noisy inductive signals.
在诱导信号(形态发生素)梯度的指导下,发育组织中会出现清晰划定的细胞类型区域,这些区域在不同的信号水平上指定不同的细胞命运。形态发生素梯度转化为离散的空间域依赖于稳定细胞位置的精确信号响应。然而,在经历形态发生和增殖的发育组织中的细胞经常经历复杂的运动,这可能会影响它们的形态发生素暴露、指定和定位。在细胞四处移动的情况下,如何实现清晰的模式?我们使用斑马鱼神经管的整体成像,分析了神经前体细胞的指定模式和运动轨迹。我们发现,在不同的 Sonic Hedgehog 信号响应下,不同命运的指定前体细胞在空间上是混合的。然后,细胞分选将它们重新排列成边界分明的区域。异位诱导的运动神经元前体细胞也能强有力地分选到正确的位置。我们的结果表明,细胞分选通过噪声诱导信号的不精确性来纠正空间模式的不准确性。