Morrow Eric M, Chen C-M Amy, Cepko Constance L
Division of Genetics, New Research Building, 77 Avenue Louis Pasteur, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Neural Dev. 2008 Jan 23;3:2. doi: 10.1186/1749-8104-3-2.
Retinal bipolar cells comprise a diverse group of neurons. Cone bipolar cells and rod bipolar cells are so named for their connections with cone and rod photoreceptors, respectively. Morphological criteria have been established that distinguish nine types of cone bipolar cells and one type of rod bipolar cell in mouse and rat. While anatomical and physiological aspects of bipolar types have been actively studied, little is known about the sequence of events that leads to bipolar cell type specification and the potential relationship this process may have with synapse formation in the outer plexiform layer. In this study, we have examined the birth order of rod and cone bipolar cells in the developing mouse and rat in vivo.
Using retroviral lineage analysis with the histochemical marker alkaline phosphatase, the percentage of cone and rod bipolar cells born on postnatal day 0 (P0), P4, and P6 were determined, based upon the well characterized morphology of these cells in the adult rat retina. In this in vivo experiment, we have demonstrated that cone bipolar genesis clearly precedes rod bipolar genesis. In addition, in the postnatal mouse retina, using a combination of tritiated-thymidine birthdating and immunohistochemistry to distinguish bipolar types, we have similarly found that cone bipolar genesis precedes rod bipolar genesis. The tritiated-thymidine birthdating studies also included quantification of the birth of all postnatally generated retinal cell types in the mouse.
Using two independent in vivo methodologies in rat and mouse retina, we have demonstrated that there are distinct waves of genesis of the two major bipolar cell types, with cone bipolar genesis preceding rod bipolar genesis. These waves of bipolar genesis correspond to the order of genesis of the presynaptic photoreceptor cell types.
视网膜双极细胞由多种神经元组成。视锥双极细胞和视杆双极细胞分别因其与视锥和视杆光感受器的连接而得名。已经建立了形态学标准，可区分小鼠和大鼠中的九种视锥双极细胞类型和一种视杆双极细胞类型。虽然双极细胞类型的解剖学和生理学方面已得到积极研究，但对于导致双极细胞类型特化的事件顺序以及该过程与外网状层突触形成可能存在的潜在关系知之甚少。在本研究中，我们检查了发育中小鼠和大鼠体内视杆和视锥双极细胞的出生顺序。
使用带有组织化学标记碱性磷酸酶的逆转录病毒谱系分析，根据成年大鼠视网膜中这些细胞特征明确的形态，确定了出生后第0天（P0）、P4和P6出生的视锥和视杆双极细胞的百分比。在这个体内实验中，我们证明视锥双极细胞的发生明显先于视杆双极细胞的发生。此外，在出生后的小鼠视网膜中，使用氚标记胸腺嘧啶核苷出生时间标记法和免疫组织化学相结合的方法来区分双极细胞类型，我们同样发现视锥双极细胞的发生先于视杆双极细胞的发生。氚标记胸腺嘧啶核苷出生时间标记研究还包括对小鼠出生后产生的所有视网膜细胞类型的出生情况进行量化。
使用大鼠和小鼠视网膜中的两种独立体内方法，我们证明了两种主要双极细胞类型存在不同的发生波，视锥双极细胞的发生先于视杆双极细胞的发生。这些双极细胞发生波与突触前光感受器细胞类型的发生顺序相对应。
