Hawley Joshua, Lea Robert, Biga Veronica, Papalopulu Nancy, Manning Cerys
Faculty of Biology Medicine and Health, The University of Manchester, Manchester M13 9PT, UK.
Biol Open. 2025 Jan 15;14(1). doi: 10.1242/bio.061765. Epub 2025 Jan 21.
In the developing mouse ventral spinal cord, HES5, a transcription factor downstream of Notch signalling, is expressed as evenly spaced clusters of high HES5-expressing neural progenitor cells along the dorsoventral axis. While Notch signalling requires direct membrane contact for its activation, we have previously shown mathematically that contact needs to extend beyond neighbouring cells for the HES5 pattern to emerge. However, the presence of cellular structures that could enable such long-distance signalling was unclear. Here, we report that cellular protrusions are present all along the apicobasal axis of individual neural progenitor cells. Through live imaging, we show that these protrusions dynamically extend and retract reaching lengths of up to ∼20 µm, enough to extend membrane contact beyond adjacent cells. The Notch ligand DLL1 was found to colocalise with protrusions, further supporting the idea that Notch signalling can be transduced at a distance. The effect of protrusions on the HES5 pattern was tested by reducing the density of protrusions using the CDC42 inhibitor ML141, leading to a tendency to decrease the distance between high HES5 cell clusters. However, this tendency was not significant and leaves an open question about their role in the fine-grained organisation of neurogenesis.
在发育中的小鼠脊髓腹侧，HES5是Notch信号通路下游的一种转录因子，它沿着背腹轴以表达HES5的神经祖细胞的均匀间隔簇的形式表达。虽然Notch信号通路的激活需要直接的膜接触，但我们之前通过数学方法表明，为了形成HES5模式，接触需要延伸到相邻细胞之外。然而，能够实现这种长距离信号传导的细胞结构的存在尚不清楚。在这里，我们报告在单个神经祖细胞的顶基轴上一直存在细胞突起。通过实时成像，我们发现这些突起会动态地伸展和收缩，长度可达约20微米，足以将膜接触延伸到相邻细胞之外。我们发现Notch配体DLL1与突起共定位，进一步支持了Notch信号通路可以在一定距离内转导的观点。通过使用CDC42抑制剂ML141降低突起的密度来测试突起对HES5模式的影响，结果导致高HES5细胞簇之间的距离有减小的趋势。然而，这种趋势并不显著，关于它们在神经发生的精细组织中的作用仍存在一个悬而未决的问题。
