小柯机器人

美国圣犹达儿童研究医院Stacey K. Ogden研究团队的研究表明，细胞神经节信号对哺乳动物的组织形态起主要调控功能。2024年1月2日出版的《细胞》杂志发表了这项成果。

为了解决形态因子传递的问题，研究人员建立了一个小鼠模型，用于研究超音速刺猬因子（SHH）形态发生器传递受损的情况；研究发现内细胞循环促进了SHH装载到细胞核的信号丝状体中。研究人员优化了保存活体细胞因子的方法，以便进行高质量显微镜观察，结果显示内源性SHH是定位在发育小鼠神经管中的细胞因子。神经管细胞因子中的SHH耗竭会改变神经元细胞的命运并影响神经发育。

丝状运动肌球蛋白10（MYO10）的突变会减少细胞因子的长度和密度，从而破坏SHH和WNT的神经元信号活动。这些结果综合证明，在哺乳动物组织发育过程中，基于细胞骨架的信号传输对形态发生器的分散起主要调控功能，并表明MYO10是细胞骨架功能的关键调节因子。

研究人员表示，在发育过程中，形态发生因子通过长距离调控细胞命运来实现组织重塑。由于无法直接观察形态发生因子的原位运输，因此确保形态发生因子成功传递的分子机制仍不清楚。

附：英文原文

Title: Cytoneme signaling provides essential contributions to mammalian tissue patterning

Author: Eric T. Hall, Miriam E. Dillard, Elizabeth R. Cleverdon, Yan Zhang, Christina A. Daly, Shariq S. Ansari, Randall Wakefield, Daniel P. Stewart, Shondra M. Pruett-Miller, Alfonso Lavado, Alex F. Carisey, Amanda Johnson, Yong-Dong Wang, Emma Selner, Michael Tanes, Young Sang Ryu, Camenzind G. Robinson, Jeffrey Steinberg, Stacey K. Ogden

Issue&Volume: 2024-01-02

Abstract: During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenous SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.

DOI: 10.1016/j.cell.2023.12.003

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01333-8