Abstract

PlexinA4 is the latest member to be identified of the PlexinA subfamily, critical transducers of class 3 semaphorin signaling as co-receptors to neuropilins 1 and 2. Despite functional information regarding the role of PlexinA4 in development and guidance of specific neuronal pathways, little is known about its distribution in the adult central nervous system (CNS). Here we report an in depth immunohistochemical analysis of PlexinA4 expression in the adult rat CNS. PlexinA4 staining was present in neurons and fibers throughout the brain and spinal cord, including neocortex, hippocampus, lateral hypothalamus, red nucleus, facial nucleus, and the mesencephalic trigeminal nucleus. PlexinA4 antibodies labeled fibers in the lateral septum, nucleus accumbens, several thalamic nuclei, substantia nigra pars reticulata, zona incerta, pontine reticular region, as well as in several cranial nerve nuclei. This constitutes the first detailed description of the topographic distribution of PlexinA4 in the adult CNS and will set the basis for future studies on the functional implications of PlexinA4 in adult brain physiology.

Highlights

  • The semaphorins are a large family of axon guidance molecules ­comprising 19 secreted and membrane bound molecules organized into eight classes (Pasterkamp and Kolodkin, 2003)

  • The present study provides the first description of PlexinA4 protein distribution in the adult rat central nervous system (CNS) using a recently developed and commercially available polyclonal antibody directed to the C-terminal sequence of mouse PlexinA4

  • We found PlexinA4 to be expressed throughout the brain of the adult rat, with highest levels in the cortex, hippocampus, brainstem, pontine and medullary nuclei and moderate levels in particular forebrain and midbrain nuclei

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Summary

Introduction

The semaphorins are a large family of axon guidance molecules ­comprising 19 secreted and membrane bound molecules organized into eight classes (Pasterkamp and Kolodkin, 2003). The best characterized of these are the class 3 semaphorins, which are secreted proteins with a diverse set of functions in developing animals including axon pruning and repulsion, dendritic attraction and branching, growth cone collapse, regulation of cell migration, and vascular remodeling (Potiron and Roche, 2005; Bussolino et al, 2006). Whereas class 3 semaphorins bind directly to either neuropilin 1 (Nrp1) or neuropilin 2 (Nrp2), signal transduction requires interaction with members of the A subfamily of Plexin co-receptors (PlexinA1–A4). PlexinA4, a type 1 membrane protein, transduces signals from semaphorin 3A and 3F (Sema3A and 3F) (Suto et al, 2003). PlexinA4 is a direct receptor and transducer for the membrane-bound class 6 semaphorins, Sema6A and 6B (Suto et al, 2005; Okada et al, 2007)

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