Targeting axons to specific fiber tracts in vivo by altering cadherin expression

In brain development, neurons have to be connected with specific postsynaptic neurons to establish functional neuronal circuits. Cadherins are cell adhesion molecules, which mark developing neuronal circuits. Each member of this class of molecules is expressed only on a restricted set of fiber fascicles that connect gray matter structures to form functional neural circuits. In view of their expression patterns, cadherins have been postulated to play a functional role in the proper establishment of fiber connections. We chose the chicken optic tectum to analyze the instructive potential of cadherins in axonal pathfinding. Three tectofugal pathways, the tectothalamic, tectobulbar, and tectoisthmic tracts, exit the dorsal mesencephalon via the brachium of the superior colliculus, a large fiber structure, which can be divided in specific subtracts that are characterized by the selective expression of N-cadherin, cadherin-7, cadherin-6B, or R-cadherin. By using in vivo electroporation, we overexpressed each of the cadherins in tectal projection neurons between embryonic days 6 and 11. Cotransfection with green fluorescent protein expression plasmid allowed us to assess the pathway choice, which the transgenic axons had made. Quantification based on confocal laser scanning microscopic images revealed that transgenic axons selectively fasciculated with tectofugal tracts specified by the matching type of cadherin. This is the first direct evidence that cadherins mediate differential axonal pathfinding in vivo, possibly by a preferentially homotypic adhesive mechanism.