Braisted J E, McLaughlin T, Wang H U, Friedman G C, Anderson D J, O'leary D D
Molecular Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Dev Biol. 1997 Nov 1;191(1):14-28. doi: 10.1006/dbio.1997.8706.
Molecular gradients have been postulated to control the topographic mapping of retinal axons in their central targets. Based initially on their expression patterns, and more recently on functional studies, members of the EphA subfamily of receptor tyrosine kinases and their ephrin-A ligands have been implicated in the guidance of retinal axons along the anterior-posterior axis of the chick optic tectum. The report that a receptor of the EphB subfamily, EphB2/Cek5/Nuk/Sek3, is expressed in a high ventral to low dorsal gradient in the developing chick retina and is present on ganglion cell axons suggests that it may be involved in the mapping of retinal axons along the corresponding dorsal-ventral axis of the tectum. To address this issue, we have determined the expression and distribution of ephrin-B1/LERK-2/Cek5-L and ephrin-B2/LERK-5/Htk-L/ELF-2, ligands for EphB2, in the developing chick retinotectal system using riboprobes, immunocytochemistry, and receptor affinity probes. Both ephrin-B1 and ephrin-B2 transcripts are expressed in a high dorsal to low ventral gradient in the developing retina, complementary to the distribution of EphB2. Ephrin-B1 and ephrin-B2 proteins are predominantly found in the developing plexiform layers, suggesting a role in the development of intraretinal connections. Neither protein is detected on ganglion cell axons. In tectum, ephrin-B1 transcripts are expressed in a high dorsal to low ventral gradient in the neuroepithelium and the protein is present along the processes of radial glia and is concentrated at their endfeet in the stratum opticum, at the time retinal axons are growing through it. This distribution of ephrin-B1 suggests that it influences retinal axon mapping along the dorsal-ventral tectal axis and may also be involved in intratectal development. In contrast, ephrin-B2 transcripts and protein are localized to the deeper retinorecipient laminae in the tectum at the time retinal axons begin to arborize in them, suggesting that this ligand may influence the laminar patterning of retinal axon terminations.
分子梯度被认为可控制视网膜轴突在其中枢靶区的拓扑映射。最初基于其表达模式，最近基于功能研究，受体酪氨酸激酶EphA亚家族的成员及其ephrin - A配体被认为参与了视网膜轴突沿鸡视顶盖前后轴的导向。有报道称，EphB亚家族的一种受体EphB2/Cek5/Nuk/Sek3在发育中的鸡视网膜中以高腹侧到低背侧的梯度表达，并存在于神经节细胞轴突上，这表明它可能参与了视网膜轴突沿顶盖相应背腹轴的映射。为了解决这个问题，我们使用核糖探针、免疫细胞化学和受体亲和探针，确定了EphB2的配体ephrin - B1/LERK - 2/Cek5 - L和ephrin - B2/LERK - 5/Htk - L/ELF - 2在发育中的鸡视网膜顶盖系统中的表达和分布。Ephrin - B1和ephrin - B2转录本在发育中的视网膜中均以高背侧到低腹侧的梯度表达，与EphB2的分布互补。Ephrin - B1和ephrin - B2蛋白主要存在于发育中的神经毡层，表明它们在视网膜内连接的发育中起作用。在神经节细胞轴突上未检测到这两种蛋白。在顶盖中，Ephrin - B1转录本在神经上皮中以高背侧到低腹侧的梯度表达，并且该蛋白沿着放射状胶质细胞的突起存在，并集中在它们位于视神经层的终足处，此时视网膜轴突正在穿过此处。Ephrin - B1的这种分布表明它影响视网膜轴突沿顶盖背腹轴的映射，也可能参与顶盖内的发育。相比之下，当视网膜轴突开始在其中分支时，Ephrin - B2转录本和蛋白定位于顶盖中较深的视网膜接受层，这表明该配体可能影响视网膜轴突终末的层状模式。
