Department of Ophthalmology & Vision Science, Institute for Regenerative Cures, Center for Neuroscience, University of California at Davis, School of Medicine, Suite 1630, Room 1617, 2921 Stockton Blvd., Sacramento, CA, 95817, USA; Department of Dermatology, University of California, Davis, CA, USA.
Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA, USA.
Dev Biol. 2021 Mar;471:97-105. doi: 10.1016/j.ydbio.2020.12.011. Epub 2020 Dec 24.
During neurulation, cranial neural crest cells (CNCCs) migrate long distances from the neural tube to their terminal site of differentiation. The pathway traveled by the CNCCs defines the blueprint for craniofacial construction, abnormalities of which contribute to three-quarters of human birth defects. Biophysical cues like naturally occurring electric fields (EFs) have been proposed to be one of the guiding mechanisms for CNCC migration from the neural tube to identified position in the branchial arches. Such endogenous EFs can be mimicked by applied EFs of physiological strength that has been reported to guide the migration of amphibian and avian neural crest cells (NCCs), namely galvanotaxis or electrotaxis. However, the behavior of mammalian NCCs in external EFs has not been reported. We show here that mammalian CNCCs migrate towards the anode in direct current (dc) EFs. Reversal of the field polarity reverses the directedness. The response threshold was below 30 mV/mm and the migration directedness and displacement speed increased with increase in field strength. Both CNCC line (O9-1) and primary mouse CNCCs show similar galvanotaxis behavior. Our results demonstrate for the first time that the mammalian CNCCs respond to physiological EFs by robust directional migration towards the anode in a voltage-dependent manner.
在神经胚形成过程中，颅神经嵴细胞（CNCC）从神经管迁移到其最终分化的部位，其迁移路径决定了颅面部的构建蓝图，而这些异常导致了四分之三的人类出生缺陷。已有研究提出，生物物理线索，如天然存在的电场（EFs），可能是 CNCC 从神经管迁移到鳃弓确定位置的引导机制之一。这种内源性 EF 可以通过生理强度的施加 EF 来模拟，据报道，施加 EF 可以引导两栖动物和鸟类的神经嵴细胞（NCC）迁移，即电趋性或电化学趋性。然而，哺乳动物 NCC 在外部 EF 中的行为尚未被报道。我们在这里展示了哺乳动物 CNCC 会朝着直流电（dc）EF 的阳极迁移。改变电场极性会使定向性发生反转。该反应的阈值低于 30mV/mm，并且随着场强的增加，定向性和迁移速度也随之增加。CNCC 系（O9-1）和原代小鼠 CNCC 都表现出类似的电趋性行为。我们的结果首次证明，哺乳动物 CNCC 以电压依赖性的方式对生理 EF 做出反应，从而朝着阳极进行强烈的定向迁移。
