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Volume 16, Number 22, Issue of November 15, 1996 pp. 7182-7192
Copyright ©1996 Society for Neuroscience

Detection of Ligands in Regions Anatomically Connected to Neurons Expressing the Eph Receptor Bsk: Potential Roles in Neuron-Target Interaction

Received April 19, 1996; revised Aug. 19, 1996; accepted Aug. 21, 1996.

Jian-Hua Zhang1, Douglas P. Cerretti2, Tian Yu1, John G. Flanagan3, and Renping Zhou1

1 Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855, 2 Immunex Research and Development Corporation, Seattle, Washington 98101, and 3 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115

Neuron-target interaction is a key feature in the establishment of neuronal networks. However, the underlying mechanism remains unclear. We have shown that at the time of target innervation, Bsk, an eph family receptor, is expressed at high levels in several brain regions including the hippocampus, olfactory bulb, and retina. To study whether the ligands are expressed in the target tissues, we investigated the expression of Bsk ligands using a ligand-affinity probe, Bsk-AP, which consisted of the extracellular domain of Bsk fused in frame with a human placental alkaline phosphatase. These analyses showed that the ligands were expressed at high levels in the developing septum, hypothalamus, olfactory neural epithelium, and tectum. In situ hybridization studies revealed that at least three different factors were responsible for the Bsk-AP binding. In the septum, Elf-1, Lerk3 (Efl-2), and AL-1/Lerk7 were transcribed. In the hypothalamus, AL-1/Lerk7 was the ligand detected by Bsk-AP. In the olfactory system, high levels of Lerk3 were detected in the sensory neurons. Both Elf-1 and AL-1/Lerk7 were present in the tectum. These ligand-positive areas are known to be anatomically connected to Bsk-expressing regions. These observations strongly suggest that Bsk and the ligands participate in neuron-target interactions in multiple systems and provide support for their involvement in topographic projection.

Key words: brain-specific kinase; growth factor receptor; eph family; alkaline phosphatase tagging; neuronal targeting; topographic projection




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