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Published online 9 October 2000. doi:10.1083/jcb.151.2.221
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© The Rockefeller University Press, 0021-9525/2000/10/221/ $5.00
The Journal of Cell Biology, Volume 151, Number 2, October 16, 2000 221-234

Original Article

A Novel Member of the Netrin Family, ß-Netrin, Shares Homology with the ß Chain of Laminin: Identification, Expression, and Functional Characterization

Manuel Kocha, Julie R. Murrellb, Dale D. Hunterb,c,d, Pamela F. Olsona,d, William Jina, Douglas R. Keenef, William J. Brunkena,e, and Robert E. Burgesona
a Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129
b Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111
c Department of Anatomy and Cell Biology, Tufts University School of Medicine, Boston, Massachusetts 02111
d Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts 02111
e Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467
f Shriners Hospital for Children, Portland, Oregon 97201

Correspondence to: Robert E. Burgeson, CBRC MGH-East Building 149, Charlestown, MA 02129. Tel:(617) 726-4186 Fax:(617) 726-4453

The netrins are a family of laminin-related molecules. Here, we characterize a new member of the family, ß-netrin. ß-Netrin is homologous to the NH2 terminus of laminin chain short arms; it contains a laminin-like domain VI and 3.5 laminin EGF repeats and a netrin C domain. Unlike other netrins, this new netrin is more related to the laminin ß chains, thus, its name ß-netrin. An initial analysis of the tissue distribution revealed that kidney, heart, ovary, retina, and the olfactory bulb were tissues of high expression. We have expressed the molecule in a eukaryotic cell expression system and made antibodies to the expressed product. Both in situ hybridization and immunohistochemistry were used to describe the cellular source of ß-netrin and where ß-netrin is deposited. ß-Netrin is a basement membrane component; it is present in the basement membranes of the vasculature, kidney, and ovaries. In addition, ß-netrin is expressed in a limited set of fiber tracts within the brain, including the lateral olfactory tract and the vomeronasal nerve. Functional studies were performed and show that ß-netrin promotes neurite elongation from olfactory bulb explants. Together, these data suggest that ß-netrin is important in neural, kidney, and vascular development.

Key Words: axon guidance, kidney, olfactory bulb, vasculature, brain


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