T-cadherin expression delineates specific regions of the developing motor axon-hindlimb projection pathway

Abstract

T-cadherin is a unique member of the cadherin family anchored to the membrane by a glycosyl phosphatidylinositol moiety (Ranscht and Dours-Zimmermann, 1991). T-cadherin's distribution in the developing motor axon pathway was mapped by immunocytochemistry in the chick lumbosacral region as spinal neurons project to and innervate hindlimb muscle. On growing motor axons, T-cadherin was expressed biphasically. Initially, uniform T-cadherin expression occurred on motor neurons as they projected between the spinal cord and the base of the hindlimb (stage 21-24), and then decreased as the axons sorted to form dorsal, ventral and muscle nerve trunks (stage 25-27). Later, as motor axons entered and formed terminal axon arbors and synapses in muscle (stages 28-36), expression reoccurred heterogeneously among motor neuron pools. Thus, T-cadherin may guide the growth and fasciculation of all motor neurons during early axon extension, but only affect particular populations during the later expression period. In the mesenchyme of the motor axon pathway, T-cadherin was restricted to regions avoided by growing axons: the posterior-half sclerotome before and during the projection of motor axons through the T-cadherin-negative anterior half, and the extrasynaptic surfaces of developing muscle. The temporal and spatial expression patterns of T-cadherin and neurite outgrowth-promoting N-cadherin were complementary both in nerve and muscle tissues. Thus, in the posterior sclerotome and in maturing muscle, T-cadherin may act as a negative regulator that works in concert with neurite growth-promoting molecules to guide motor axons to their peripheral targets.