A variety of molecular influences in the extracellular matrix (ECM) interac
t with developing axons to guide the formation of hippocampal axon pathways
. One of these influences may be chondroitin sulfate proteoglycans (CSPGs),
which are known to inhibit axonal extension during development and followi
ng central nervous system injury. In this study, we examined the role of CS
PGs and cell adhesion molecules in the regulation of axon tract formation d
uring hippocampal development. We used indirect immunofluorescence to exami
ne the developmental pattern of CSPG expression relative to axon tracts tha
t express the cell adhesion molecule LI. Additionally, we used dissociated
and explant cell cultures to examine the effects of CSPGs on hippocampal ax
on development in vitro. In vivo we found that the CSPG neurocan is express
ed throughout the alveus, neuropil layers, and parts of the dentate gyrus f
rom E16 to P2. The CSPG phosphacan is expressed primarily in the neuropil l
ayers at postnatal stages. After E18, intense labeling of neurocan was obse
rved in regions of the alveus surrounding L1-expressing axon fascicles. In
vitro, axons from brain regions that project through the alveus during deve
lopment would not grow across CSPG substrate, in a concentration-dependent
manner. In addition, hippocampal axons from dissociated neuron cultures onl
y traveled across CSPG substrata as fasciculated axon bundles. These findin
gs implicate CSPG in the regulation of axon trajectory and fasciculation du
ring hippocampal axon tract formation. (C) 2000 Wiley-Liss, Inc.