Netrins are secreted proteins that serve as potent axon guidance molecules
in vertebrates and invertebrates. We report the identification of a novel m
ammalian member of this family. Netrin-4 is similar in predicted size and s
econdary structure to the other three netrins; all contain, in order, an am
ino-terminal signal sequence, a laminin-type globular domain of the 'VI' ty
pe, three laminin-type epidermal growth factor (EGF) repeats, and a carboxy
l-terminal 'netrin module'. In terms of primary sequence, however, netrin-4
is a distant relative of netrins-1-3, and its globular domain is more clos
ely related to those of laminins than to those of other netrins. Netrin-4 i
s broadly expressed in both neural and non-neural tissues of embryonic and
adult mice. In embryonic spinal cord, it is selectively expressed by cells
at the lateral margins of the floor plate. In postnatal brain, it is select
ively expressed in subsets of neurons, including cerebellar granule and hip
pocampal pyramidal cells. (C) 2000 Elsevier Science Ireland Ltd. All rights
reserved.