Development of nodal and paranodal membrane specializations in amphibian peripheral nerves

Abstract

Peripheral nerves from the hind legs of frog tadpoles were examined in order to ascertain the pattern of development of nodal and paranodal specializations in myelinated fibers. In thin sections the earliest detectable node-related specializations resemble ‘intermediate’ junctions between axons and Schwann cell processes. These occur in individually ensheathed axons near the edges of the sheath segments and could represent early nodal or paranodal components or transient structures. The characteristic nodal ‘undercoating’ is indistinct and highly variable in thickness in immature fibers and its density is lower in developing nodes than in adult nodes. Corresponding freeze-fracture replicas of developing axons demonstrate aggregates of nodal E face particles whose concentration is lower than that in the adult. Such aggregates usually occur immediately adjacent to Schwann cell indentations, even though early in development the latter may not exhibit the paracrystalline pattern seen in the adult paranodal axolemma. On rare occasions, node-like particle aggregates and presumptive nodal undercoatings have been observed without recognizable paranodal junctions or indentations nearby. However, neither specialization has been found in axons not individually ensheathed by Schwann cells. Paranodal Schwann cell loops are widely separated and irregularly arranged in the developing nodes, and the paranodal regions flanking a node usually mature asymmetrically. Differentiated paranodal junctions appear early in axons ensheathed by only a few loose Schwann cell lamellae. However, such junctions are not formed by all paranodal loops; they consistently appear first in the loops close to the node and only later in those further removed. No junctional specialization has been observed in either the axolemma or the Schwann cell membrane without the close association of the other. Our results indicate that both nodal and paranodal specializations appear early in development and mature gradually together and that the axon and the Schwann cell are consistently in close association where node-related specializations appear. No evidence of ‘independent’ differentiation in either partner was observed.