Departament de Física de la Matèria Condensada, Facultat de Física, Universitat de Barcelona, 08028 Barcelona, Spain.
Universitat de Barcelona Institute of Complex Systems (UBICS), Universitat de Barcelona, 08028 Barcelona, Spain.
Development. 2022 Aug 1;149(15). doi: 10.1242/dev.200510. Epub 2022 Jul 28.
In animals and plants, stem-cell niches are local microenvironments that are tightly regulated to preserve their unique identity while communicating with adjacent cells that will give rise to specialized cell types. In the primary root of Arabidopsis thaliana, two transcription factors, BRAVO and WOX5, among others, are expressed in the stem-cell niche. Intriguingly, BRAVO, a repressor of quiescent center divisions, confines its own gene expression to the stem-cell niche, as evidenced in a bravo mutant background. Here, we propose through mathematical modeling that BRAVO confines its own expression domain to the stem-cell niche by attenuating a WOX5-dependent diffusible activator of BRAVO. This negative feedback drives WOX5 activity to be spatially restricted as well. The results show that WOX5 diffusion and sequestration by binding to BRAVO are sufficient to drive the experimentally observed confined BRAVO expression at the stem-cell niche. We propose that the attenuation of a diffusible activator can be a general mechanism acting at other stem-cell niches to spatially confine genetic activity to a small region while maintaining signaling within them and with the surrounding cells.
在动植物中,干细胞龛位是局部微环境,受到严格调控以保持其独特的身份,同时与将产生特化细胞类型的相邻细胞进行通讯。在拟南芥的初生根中,除其他转录因子外,BRAVO 和 WOX5 也在干细胞龛位中表达。有趣的是,BRAVO 是静止中心分裂的抑制剂,其自身的基因表达局限于干细胞龛位,这在 bravo 突变体背景中得到了证实。在这里,我们通过数学建模提出,BRAVO 通过衰减依赖于 WOX5 的 BRAVO 可扩散激活剂来将其自身的表达域限制在干细胞龛位中。这种负反馈作用也使 WOX5 活性受到空间限制。结果表明,WOX5 的扩散和与 BRAVO 的结合足以驱动实验观察到的在干细胞龛位处 BRAVO 的受限表达。我们提出,一种可扩散激活剂的衰减可以是一种普遍机制,作用于其他干细胞龛位,将遗传活性限制在一个小区域内,同时保持它们内部以及与周围细胞之间的信号传递。