Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Curr Biol. 2011 Feb 22;21(4):278-87. doi: 10.1016/j.cub.2011.01.015. Epub 2011 Jan 27.
In both vertebrates and invertebrates, developing organs and tissues must be precisely patterned. One patterning mechanism is Notch/Delta-mediated lateral inhibition. Through the process of lateral inhibition, Drosophila sensory organ precursors (SOPs) are selected and sensory bristles form into a regular pattern. SOP cell fate is determined by high Delta expression and following expression of neurogenic genes like neuralized. SOP selection is spatially and temporally regulated; however, the dynamic process of precise pattern formation is not clearly understood.
In this study, using live-imaging analysis, we show that the appearance of neuralized-positive cells is random in both timing and position. Excess neuralized-positive cells are produced by developmental errors at several steps preceding and accompanying lateral inhibition. About 20% of the neuralized-positive cells show aberrant cell characteristics and high Notch activation, which not only suppress neural differentiation but also induce caspase-dependent cell death. These cells never develop into sensory organs, nor do they disturb bristle patterning.
Our study reveals the incidence of developmental errors that produce excess neuralized-positive cells during sensory organ development. Notch activation in neuralized-positive cells determines aberrant cell fate and typically induces caspase-dependent cell death. Apoptosis is utilized as a mechanism to remove cells that start neural differentiation at aberrant positions and timing and to ensure robust spacing pattern formation.
在脊椎动物和无脊椎动物中,发育中的器官和组织必须精确地形成模式。一种模式形成机制是 Notch/Delta 介导的侧向抑制。通过侧向抑制过程,果蝇感觉器官前体细胞(SOP)被选择,感觉刚毛形成规则的图案。SOP 细胞命运由高 Delta 表达和随后的神经基因表达如 neuralized 决定。SOP 的选择在空间和时间上受到调节;然而,精确模式形成的动态过程尚不清楚。
在这项研究中,我们通过活体成像分析表明,neuralized 阳性细胞的出现无论是在时间还是位置上都是随机的。在侧向抑制之前和伴随的几个步骤中,发育错误会产生过多的 neuralized 阳性细胞。大约 20%的 neuralized 阳性细胞表现出异常的细胞特征和高 Notch 激活,这不仅抑制神经分化,还诱导半胱天冬酶依赖性细胞死亡。这些细胞永远不会发育成感觉器官,也不会干扰刚毛模式形成。
我们的研究揭示了在感觉器官发育过程中产生过多 neuralized 阳性细胞的发育错误的发生率。neuralized 阳性细胞中的 Notch 激活决定了异常的细胞命运,并通常诱导半胱天冬酶依赖性细胞死亡。细胞凋亡被用作一种机制,以去除在异常位置和时间开始神经分化的细胞,并确保强大的间隔模式形成。