Kramer P R, Wray S
Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Genes Dev. 2000 Jul 15;14(14):1824-34.
Although a variety of cues have been implicated in axonal targeting during embryogenesis and regeneration, the precise mechanisms guiding olfactory axons remain unclear. Appropriate olfactory axon pathfinding is essential for functional chemoreceptive and pheromone receptive systems. Olfactory axon pathfinding is also necessary for establishment of the neuroendocrine LHRH system, cells critical for reproductive function. LHRH cells exhibit neurophilic migration moving from the nasal region along olfactory axons into the brain. Factors involved in the migration of these neuroendocrine cells are as yet unresolved. We report identification of a novel factor termed nasal embryonic LHRH factor (NELF) that was discovered in a differential screen of migrating versus nonmigrating primary LHRH neurons. NELF is expressed in PNS and CNS tissues during embryonic development, including olfactory sensory cells and LHRH cells. NELF antisense experiments indicate that a reduction in NELF expression decreases olfactory axon outgrowth and the number of LHRH neurons that migrate out of the nasal tissue. These results demonstrate that NELF plays a role as a common guidance molecule for olfactory axon projections and subsequently, either directly or indirectly, in the neurophilic migration of LHRH cells.
尽管在胚胎发育和再生过程中，多种线索与轴突靶向有关，但引导嗅觉轴突的精确机制仍不清楚。适当的嗅觉轴突寻路对于功能性化学感受和信息素感受系统至关重要。嗅觉轴突寻路对于神经内分泌促性腺激素释放激素（LHRH）系统的建立也是必要的，该系统的细胞对生殖功能至关重要。LHRH细胞表现出嗜神经性迁移，从鼻腔区域沿着嗅觉轴突进入大脑。参与这些神经内分泌细胞迁移的因素尚未明确。我们报告了一种名为鼻腔胚胎LHRH因子（NELF）的新因子的鉴定，该因子是在对迁移的和未迁移的原代LHRH神经元进行差异筛选时发现的。NELF在胚胎发育过程中在周围神经系统（PNS）和中枢神经系统（CNS）组织中表达，包括嗅觉感觉细胞和LHRH细胞。NELF反义实验表明，NELF表达的降低会减少嗅觉轴突的生长以及从鼻腔组织迁移出的LHRH神经元的数量。这些结果表明，NELF作为嗅觉轴突投射的共同引导分子发挥作用，随后直接或间接地在LHRH细胞的嗜神经性迁移中发挥作用。
