Hh signaling has been shown to be activated in intact and injured peripheral nerve. However, the role of Hh signaling in peripheral nerve is not fully understood. In the present study, we observed that Hh signaling responsive cells [Gli1(+) cells] in both the perineurium and endoneurium. In the endoneurium, Gli1(+) cells were classified as blood vessel associated or non-associated. After injury, Gli1(+) cells around blood vessels mainly proliferated to then accumulate into the injury site along with endothelial cells. Hh signaling activity was retained in Gli1(+) cells during nerve regeneration. To understand the role of Hedgehog signaling in Gli1(+) cells during nerve regeneration, we examined mice with Gli1(+) cells-specific inactivation of Hh signaling (Smo cKO). After injury, Smo cKO mice showed significantly reduced numbers of accumulated Gli1(+) cells along with disorganized vascularization at an early stage of nerve regeneration, which subsequently led to an abnormal extension of the axon. Thus, Hh signaling in Gli1(+) cells appears to be involved in nerve regeneration through controlling new blood vessel formation at an early stage.

Hh 信号已显示在完整和受损的周围神经中被激活。然而，Hh 信号在周围神经中的作用尚不完全清楚。在本研究中，我们观察到神经束膜和神经内膜中的 Hh 信号响应细胞 [Gli1(+) 细胞]。在神经内膜中，Gli1(+) 细胞被分类为血管相关或非相关。损伤后，血管周围的Gli1(+)细胞主要增殖，然后与内皮细胞一起聚集到损伤部位。在神经再生过程中，Gli1(+) 细胞中保留了 Hh 信号活动。为了了解 Hedgehog 信号在神经再生过程中 Gli1(+) 细胞中的作用，我们检查了具有 Gli1(+) 细胞特异性 Hh 信号失活 ( Smo cKO ) 的小鼠。受伤后，Smo cKO小鼠在神经再生的早期阶段表现出积累的 Gli1(+) 细胞数量显着减少以及血管化紊乱，随后导致轴突异常延伸。因此，Gli1(+) 细胞中的 Hh 信号似乎通过在早期控制新血管形成而参与神经再生。