LOCALIZATION OF EXTRACELLULAR-MATRIX MOLECULES, INTEGRINS AND THEIR REGULATORS, TGF BETA-S, IS CORRELATED WITH AXON PATHFINDING IN THE SPINAL-CORD OF NORMAL AND DANFORTHS SHORT TAIL MICE

To clarify the roles of extracellular matrix molecules (ECMs) and thei r receptors, integrins, in axonal pathfinding, their spatiotemporal lo calization was studied immunohistochemically in the developing mouse s pinal cord. Immunoreactivities for collagen type IV (Col IV), laminin, integrins (alpha 2, alpha 3 and beta 1 subunits), and transforming gr owth factor (TGF) beta s (TGF beta 2 and TGF beta 3), putative regulat ors of gene expression of these molecules, were localized on the midli ne of the ventral spinal cord, or the 'floor plate', in normal ICR mic e. These immunoreactions appeared at embryonic day 9 (E9), when commis sural axons began to cross the floor plate, and peaked at E13-E14 when more axons crossed, turned rostrally, and projected longitudinally. A t this stage, TAG-1-immunopositive commissural axons passed through th e floor plate region. Longitudinal axons, on the other hand, projected ipsilaterally parallel to the midline. Immunoreactions for ECMs, inte grins and TGF beta s were weakly positive at the midline until postnat al day 0 (P0), after which they decreased markedly. In Danforth's shor t tail (Sd) heterozygous mutants with discontinuous floor plates, immu noreactions for ECMs, integrins, and TGF beta s were not detected at P 0. Few crossing axons were seen at this stage, and longitudinally asce nding axons crossed via aberrant paths in these regions. These results suggest that the restricted localization of ECMs, integrins, and TGF beta s at the floor plate is involved in the pathfinding of commissura l and longitudinal axons. (C) 1997 Elsevier Science B.V.