Holash J A, Soans C, Chong L D, Shao H, Dixit V M, Pasquale E B
Burnham Institute, La Jolla, California 92037, USA.
Dev Biol. 1997 Feb 15;182(2):256-69. doi: 10.1006/dbio.1996.8496.
Recent evidence suggests that Eph receptor tyrosine kinases and their ligands provide positional information in the developing visual system. We previously found that the Eph receptor Cek5 is more highly expressed in the ventral than dorsal chicken embryonic retina. We now report the identification of a chicken ligand for Cek5 (cCek5-L) that is 75% identical to the ligand LERK2. In situ hybridization experiments do not reveal a dorsoventral gradient of cCek5-L transcripts in the optic tectum at Embryonic Day 8, suggesting that this ligand is not involved in guiding Cek5-expressing axons in the tectum. Surprisingly, it is in the retina that high levels of cCek5-L mRNA are present. In the early retina, cCek5-L is more highly expressed in the dorsal than the ventral aspect. Similarly, a Cek5 Ig chimera labels dorsal but not ventral retina, indicating that even if several Cek5 ligands are present, their overall distribution is complementary to that of Cek5. Hence, Cek5 and cCek5-L may both contribute to define anatomical compartments within the early retina. In contrast, in the 11-day embryonic retina the distributions of Cek5 and its ligand(s) show considerable overlap, suggesting changing functions as development progresses. In dissociated cultures of dorsal or ventral retinal cells seeded on plates coated with either receptor or ligand Ig chimeras, the interaction between Cek5 and its ligand(s) or cCek5-L and its receptor(s) is sufficient to mediate cell adhesion and allows neurite outgrowth.
最近的证据表明，Eph受体酪氨酸激酶及其配体在发育中的视觉系统中提供位置信息。我们先前发现，Eph受体Cek5在鸡胚视网膜腹侧的表达高于背侧。我们现在报告鉴定出一种Cek5的鸡配体（cCek5-L），它与配体LERK2有75%的同源性。原位杂交实验未揭示胚胎第8天视顶盖中cCek5-L转录本的背腹梯度，这表明该配体不参与引导视顶盖中表达Cek5的轴突。令人惊讶的是，高水平的cCek5-L mRNA存在于视网膜中。在早期视网膜中，cCek5-L在背侧的表达高于腹侧。同样，一种Cek5免疫球蛋白嵌合体标记背侧而非腹侧视网膜，这表明即使存在几种Cek5配体，它们的总体分布与Cek5互补。因此，Cek5和cCek5-L可能都有助于确定早期视网膜内的解剖分区。相比之下，在11天的胚胎视网膜中，Cek5及其配体的分布有相当大的重叠，这表明随着发育的进行功能在发生变化。在接种于包被有受体或配体免疫球蛋白嵌合体的培养板上的背侧或腹侧视网膜细胞的解离培养物中，Cek5与其配体或cCek5-L与其受体之间的相互作用足以介导细胞黏附并促进神经突生长。
