GRADED AND LAMINA-SPECIFIC DISTRIBUTIONS OF LIGANDS OF EPHB RECEPTOR TYROSINE KINASES IN THE DEVELOPING RETINOTECTAL SYSTEM

Molecular gradients have been postulated to control the topographic ma pping of retinal axons in their central targets. Based initially on th eir expression patterns, and more recently on functional studies, memb ers of the EphA subfamily of receptor tyrosine kinases and their ephri n-A ligands have been implicated in the guidance of retinal axons alon g the anterior-posterior axis of the chick optic tectum. The report th at a receptor of the EphB subfamily, EphB2/Cek5/Nuk/ Sek3, is expresse d in a high ventral to low dorsal gradient in the developing chick ret ina and is present on ganglion cell axons suggests that it may be invo lved in the mapping of retinal axons along the corresponding dorsal-ve ntral axis of the tectum. To address this issue, we have determined th e 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 retino tectal system using riboprobes, immunocytochemistry, and receptor affi nity probes. Both ephrin-B1 and ephrin-B2 transcripts are expressed in a high dorsal to low ventral gradient in the developing retina, compl ementary to the distribution of EphB2. Ephrin-B1 and ephrin-B2 protein s are predominantly found in the developing plexiform layers, suggesti ng a role in the development of intraretinal connections. Neither prot ein is detected on ganglion cell axons. In tectum, ephrin-B1 transcrip ts are expressed in a high dorsal to low ventral gradient in the neuro epithelium and the protein is present along the processes of radial gl ia and is concentrated at their endfeet in the stratum opticum, at the time retinal axons are growing through it. This distribution of ephri n-B1 suggests that it influences retinal axon mapping along the dorsal -ventral tectal axis and may also be involved in intratectal developme nt. In contrast, ephrin-B2 transcripts and protein are localized to th e deeper retinorecipient laminae in the tectum at the time retinal axo ns begin to arborize in them, suggesting that this ligand may influenc e the laminar pattering of retinal axon terminations. (C) 1997 Academi c Press.