躯体感觉神经元是动物和人感知机械、温度以及伤害性刺激的关键组成部分。目前人们对于躯体感觉神经元发育分子机制的认识仍不充分。项目预实验发现在一个斑马鱼突变品系中，幼年突变动物对振动刺激的反应显著增强。此品系中所突变的ETGP基因只存在于脊椎动物。在斑马鱼及小鼠中ETGP基因均特异地在躯体感觉神经元中表达。在大鼠PC12细胞株中消减ETGP功能可显著加快神经生长因子所诱导的神经突起生长；而在斑马鱼突变动物中，躯体感觉神经元的轴突生长出现显著异常。本项目利用斑马鱼模式动物，通过对躯体感神经元发育与感觉行为的考察来明确ETGP基因在整体动物中的功能作用。项目还将开展对ETGP蛋白功能的研究，采用PC12细胞神经突起生长与斑马鱼躯体感神经元轴突生长为研究模型，用以明确ETGP蛋白在躯体感神经元发育中作用的分子机制。项目研究的实施亦将有助于对遗传性感觉神经病变分子基础的理解。

Somatosensory neurons are critical components of the sensory system that processes the mechanical, temperature, and nociceptive stimuli in both animal and human. Molecular mechanisms underlying somatosensory neuron development are currently not well understood. We discovered a zebrafish mutant which produced fish larvae that showed elevated response to vibration stimulus. ETGP, the gene disrupted in the mutant is evolutionally conserved in the vertebrates only. In both the zebrafish and the mouse ETGP is specifically expressed in the somatosensory neurons. In rat PC12 cells, inhibition of ETGP function by RNA interference significantly accelerated nerve growth factor-induced differentiation and neurite outgrowth. In zebrafish ETGP mutant animals, the periphery axons of the somatosensory neurons developed abnormal outgrowth. The proposed project will examine the somatosensory neuron development and sensory-related behaviors in the zebrafish model in order to elucidate the functional roles of ETGP at the whole organism level. The project will also investigate the molecular mechanisms regulating ETGP’s functions in the neurite outgrowth of the PC12 cells and the somatosensory neurons in the zebrafish. In addition, the proposed studies should provide insights into mechanisms of disease in hereditary sensory neuropathies.