Developmental Brain Research 143 (2003) 1–13 www.elsevier.com / locate / devbrainres Research report Developmental distribution of coxsackie virus and adenovirus receptor localized in the nervous system a,b a b a, * Yuko Hotta , Takao Honda , Makoto Naito , Ryozo Kuwano a Department of Molecular Genetics, Genome Science Branch, Center for Bioresource-based Researches, Brain Research Institute, Niigata University, Niigata, Japan b Department of Cellular Function, Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences,1-757 Asahimachi, Niigata 951-8510, Japan Accepted 4 February 2003 Abstract Mouse coxsackie virus and adenovirus receptor (mCAR), which was isolated from the nerve growth cone-enriched fraction of newborn mouse brains, is a member of immunoglobulin-super family, and functions as a homophilic adhesion molecule. We observed the expression of mCAR in embryos to adult tissues by means of immunohistochemical analysis with a peptide antibody. mCAR expression was first detected in the embryonic ectoderm in the uterus on embryonic day 6.5 (E6.5). Then it was strongly expressed in the neuroepithelium of the neural tube, the developing brain and the spinal cord from E8.5 to postnatal day 7 (P7), in the cranial motor nerves from E9.5 to E11.5, and in the optic nerve from E13.5 to P7, which agrees with periods of their respective morphogenetic peaks. This expression of mCAR decreased postnatally and was absent in adult tissues. We found that mCAR occurred in a few proliferating cells of the hippocampal dentate gyrus, the subventricular zone (SVZ) of the lateral ventricles, and the rostral migratory stream (RMS) over P21. These observations demonstrate that mCAR was expressed characteristically in the immature neuroepithelium including progenitor cells or radial cells derived from the neural tube and in immature cells in a selected germinal zone of the mature brain. Based on our findings, we propose that mCAR is involved in migration and fasciculation during a restricted period as an adhesion molecule.  2003 Elsevier Science B.V. All rights reserved. Keywords: Coxsackie virus; Adenovirus receptor; Nervous system 1. Introduction hydrophobic transmembrane domain, and a long cyto- plasmic domain consisting of 107 amino acids, mCAR A membrane protein with a molecular mass of 46 kDa belongs to the immunoglobulin superfamily, and exhibits was purified from the growth cone-enriched fraction of homophilic adhesion activity [20] similar to SC1, L1and newborn mouse brains [1], and identified as a mouse NCAM. Cell adhesion molecules in the central nervous coxsackievirus and adenoviruses receptor (mCAR) system may regulate developmental processes such as [5,6,9,30]. The predominant expression of mCAR was axonal guidance, fasciculation, and synapse formation observed in the nervous system where it increased during [16]. SC1 transiently expressed on spinal cord early in the embryonic stage but decreased rapidly after birth, as development [29]. L1 is expressed in optic nerve from judged on Western and Northern blot analyses, and in situ embryonic day 15 through adulthood [4]. NCAM-H, a hybridization [20]. highly polysialylated NCAM, in the central nervous sys- Due to its structural features, i.e., an extra cellular tem is associated not only with neural development, but domain containing two disulfide-linked loops, a typical also with adult functions such as processing and neuronal plasticity [26]. These adhesion molecules express in differ- ent periods and several places, then disappear and some- where reappear. We examined whether or not mCAR expression was synchronized with neuronal maturation and *Corresponding author. Tel.: 181-25-227-2344; fax: 181-25-227- network formation. 0793. E-mail address: ryosun@gene.med.niigata-u.ac.jp (R. Kuwano). During development, an increasing proportion of neuro- 0165-3806 / 03 / $ – see front matter  2003 Elsevier Science B.V. All rights reserved. doi:10.1016 / S0165-3806(03)00035-X