Martinez-Marcos A, Jia C, Quan W, Halpern M
Departamento de Ciencias Médicas, Facultad de Medicina, Centro Regional de Investigación Biomédica, Universidad de Castilla-la Mancha, Avda. Almansa S/N, 02006 Albacete, Spain.
J Neurobiol. 2005 Jun;63(3):173-87. doi: 10.1002/neu.20128.
The location of neurogenesis and the direction of migration of neurons in the adult mouse vomeronasal organ is controversial. Cell division occurs at the center, and particularly, at the edges of the epithelium. Newly generated cells at the center of the epithelium participate in neurogenesis, however, it is unknown to what extent dividing cells at the edges participate in growth, become apoptotic or mature into neurons. Premitotic cells were labeled with bromodeoxyuridine (BrdU) in adult mice and animals allowed to survive for different postinjection periods. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end-labeling (TUNEL) method was used to show the distribution of apoptotic cells. The vertical and horizontal position of BrdU-labeled cells was analyzed as a function of postinjection survival time. Vertical and horizontal migration of BrdU-labeled cells were detected. Cells in the central portions of the epithelium migrated vertically to become neurons as demonstrated by co-expression of olfactory marker protein. Cells at the edges migrated horizontally very slowly (less than 10% of the distance from the edge to the center of the epithelium per month), thus indicating that these cells participate in cell renewal exclusively in marginal regions. Neural turnover in the mouse vomeronasal epithelium, therefore appears to occur through a process of vertical migration. Data on the distribution of apoptotic cells indicate that a number of dividing cells throughout the epithelium, but particularly at the edges, die before becoming functional neurons. Accordingly, most dividing cells at the edges probably constitute a reservoir of stem cells dying before differentiation.
成年小鼠犁鼻器中神经发生的位置以及神经元迁移的方向存在争议。细胞分裂发生在上皮组织的中央,尤其是边缘部位。上皮组织中央新生成的细胞参与神经发生,然而,边缘部位正在分裂的细胞在多大程度上参与生长、发生凋亡或成熟为神经元尚不清楚。在成年小鼠中用溴脱氧尿苷(BrdU)标记有丝分裂前期细胞,并让动物在注射后存活不同时期。采用末端脱氧核苷酸转移酶介导的生物素化dUTP缺口末端标记法(TUNEL)来显示凋亡细胞的分布。分析BrdU标记细胞的垂直和水平位置与注射后存活时间的关系。检测到BrdU标记细胞的垂直和水平迁移。上皮组织中央部分的细胞垂直迁移成为神经元,这通过嗅觉标记蛋白的共表达得以证明。边缘部位的细胞水平迁移非常缓慢(每月迁移距离小于从边缘到上皮组织中央距离的10%),因此表明这些细胞仅在边缘区域参与细胞更新。所以,小鼠犁鼻上皮中的神经更替似乎是通过垂直迁移过程发生的。关于凋亡细胞分布的数据表明,上皮组织中许多正在分裂的细胞,尤其是边缘部位的细胞,在成为功能性神经元之前死亡。因此,边缘部位大多数正在分裂的细胞可能构成了在分化前死亡的干细胞库。