MATURATION-DEPENDENT UP-REGULATION OF GROWTH-PROMOTING MOLECULES IN DEVELOPING CORTICAL PLATE CONTROLS THALAMIC AND CORTICAL NEURITE GROWTH

We have tested the hypothesis that maturation-dependent changes in the cortical plate affect the spatiotemporal growth patterns of developin g thalamocortical and corticocortical axonal projections, Given a choi ce between alternating lanes of embryonic (E18-19) and neonatal (P0-1) rat cortical plate membranes, embryonic (E18-19) thalamic and cortica l neurites prefer to extend on neonatal membranes, Thalamic and cortic al explants do extend neurites on uniform carpets of E19 cortical plat e membranes, but the outgrowth is consistently greater on uniform carp ets of P1 cortical plate membranes, These experiments demonstrate a ma turation-dependent enhancement in the ability of cortical plate to sup port neurite growth from thalamic and cortical explants. In contrast, retinal and cerebellar neurites, which do not grow into cortex in vivo , generally grew poorly on these membranes, suggesting a degree of spe cificity to the neurite growth response, Immunohistochemical analysis of developing cortex suggests that several extracellular matrix (ECM) and cell adhesion molecules are upregulated in cortical plate, However , immunocharacterization of membrane carpets for these same ECM and ce ll adhesion molecules suggests that the growth preferences of thalamic and cortical neurites in vitro are predominantly influenced by membra ne-anchored, rather than ECM, molecules. Western analysis of E19 and P 1 cortical plate membranes supports this conclusion, and indicates tha t the membrane-anchored cell adhesion molecules L1 and N-CAM are more abundant in the P1 cortical plate membrane preparation, Experiments in which cortical plate membranes were treated to remove molecules sensi tive to phosphatidylinositol (PI)-specific phospholipase C demonstrate that neurite growth promoters present in E19 cortical plate membranes are predominantly PI linked, whereas those present in P1 membranes ar e predominantly non-PI linked, These findings indicate that the neurit e growth preferences are mediated, at least in part, by an upregulatio n of neurite growth-promoting molecules in developing cortical plate t hat are not PI linked, Taken together, these findings suggest that a m aturation-dependent upregulation of neurite growth-promoting molecules on cortical plate cells controls the invasion of the cortical plate b y thalamocortical and corticocortical axons.