Ž . Molecular Brain Research 47 1997 202–214 Research report Dynamic expression suggests multiple roles of the eph family receptor ž / brain-specific kinase Bsk during mouse neurogenesis Jian-Hua Zhang a , Aurea F. Pimenta b , Pat Levitt b , Renping Zhou a, ) a Laboratory for Cancer Research, College of Pharmacy, Rutgers UniÕersity, Piscataway, NJ 08854, USA b Department of Neuroscience and Cell Biology, UniÕersity of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA Accepted 17 December 1996 Abstract The eph family ligands and receptors have been implicated in mediating topographic neuron-target interactions. We recently isolated Bsk, a new member of the eph family receptors, and showed that it is expressed primarily in the brain. To investigate the role of Bsk in the development of the nervous system, we examined the temporal and spatial patterns of Bsk expression using in situ hybridization. We report here that Bsk expression exhibits dynamic changes during embryogenesis. In early embryos, Bsk is widely transcribed in the nervous system, including the forebrain, midbrain, hindbrain and spinal cord. Bsk expression in the midbrain, hindbrain and spinal cord, however, gradually decreases while in the forebrain increases over time. By embryonic day 18, the most intense Bsk expression was found in the limbic system. High levels of the expression in the limbic system persisted throughout post-natal development and remained stable in the adult up to 24 month. The topography of Bsk expression is in the form of gradients in several regions of the brain, including the lateral septum, spinal cord, as well as the hippocampus. Selective expression was also observed in Purkinje cells. Our findings on the topography of Bsk expression provide support to potential roles of Bsk in topographic projection. Our analyses further suggest that there may be other novel functions of Bsk in early neurogenesis in addition to potential roles in topographic mapping. q 1997 Elsevier Science B.V. All rights reserved. Keywords: Eph family receptor; Hybridization, in situ; Neurogenesis; Limbic system; Topographic projection; Axonal guidance 1. Introduction Ž . Receptor tyrosine kinases RTKs mediate the biologi- cal effects of many growth factors in the nervous system. For example, the trk family receptors are essential for wx neurotrophin-mediated survival of neurons 4 . To study the function of RTKs in the development of the nervous system, we recently isolated a receptor tyrosine kinase, w x designated Bsk, from a mouse brain cDNA library 35 . The chicken, rat and human homologs of Bsk were inde- w x pendently isolated and named cek7 22,24 , Ehk-1rRek7 w x w x 16,28,32 and HEK7 10 . Bsk belongs to the eph family of receptor tyrosine kinases, the largest group of known w x RTKs 30 . Like Bsk, many of the eph family members are expressed in the developing and adult neural tissues, sug- ) Ž . Corresponding author. Fax: q1 908 445-0687; E-mail: rzhou@rci.rutgers.edu gesting that they play important roles in the development w x and maintenance of the nervous system 7,10,13,16,30,31 . Eph family ligands and receptors have been implicated Ž in specific aspects of nervous system assembly reviewed w x. in 3,11,29 . The repulsive axonal guidance signal Ž . RAGS , isolated as an activity guiding the projection of retinal axons, is a candidate ligand of Rek7, a rat homolog w x of Bsk 32 . A related ligand, Elf-1, isolated based on its ability to interact with Mek4, Sek and the chicken Bsk w x homolog, Cek7 receptors 5,23 , is also implicated in the w x development of retinotectal topographic projections 6,18 . Elf-1 and one of its candidate receptors, Mek4 are ex- pressed in matching gradients in tectum and retina, respec- tively, suggesting a role in establishing topographic retino- wx tectal connections 6 . Furthermore, Elf-1 selectively repels topographically incorrect retinal axons while allows the w x growth of the correct axons 18 . Consistent with these observations, Bsk and its ligands are expressed in the hippocampus and its target tissue, the lateral septum, re- 0169-328Xr97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0169-328X 97 00051-X