[Molecular mechanisms of the pathway formation in the fetal rat cerebral neocortex].

Neural cell adhesion molecules (NCAMs), L1 and TAG-1, which are prominently expressed in the developing nervous system, have been shown to promote axonal growth and bundle formation of central neurons in vitro. In the cerebral neocortex of fetal rats, immunoreactions of L1 and TAG-1 were specifically localized on thalamic afferent axons and cortical efferent axons, respectively. L1-bearing thalamocortical axons preferentially extended in the subplate of the cortical anlage where neurocan, a brain-specific chondroitin sulfate proteoglycan (CSPG), was prominently expressed. In contrast, cortical efferent axons immunoreactive for TAG-1 did not enter the subplate and run in the intermediate zone where neurocan expression was less abundant. In addition, TAG-1-bearing axons extensively invaded regions expressing another type of brain-specific CSPG, phosphacan. In the cell culture system, neurite outgrowth of TAG-1-transfected PC 12 D cells was remarkably inhibited on the neurocan substrate, while the outgrowth on phosphacan substrate was significantly promoted. Although both L1 and TAG-1 have been reported to bind both neurocan and phosphacan in vitro, interactions between NCAMs and CSPGs in vivo indicate more complicated patterns than previously thought. Thus, the present results suggest that various patterns of functional correlation between NCAMs and CSPGs play important roles in the pathway formation of the rat cerebral neocortex.