Guidance of regenerating motor axons in larval and juvenile bullfrogs

Abstract

The segmental distribution of regenerating bullfrog motor axons was mapped in advanced tadpoles and juvenile frogs by stimulating selected muscle nerves and recording from the distal ends of the 3 lumbar ventral roots (VRs) that innervate the hindlimb. When motoneurons were axotomized by VR transection, they reestablished their original innervation fields, rarely, if ever, growing beyond the territory normally supplied by their spinal segment. However, when motoneurons were axotomized in the spinal nerves at the level of the hindlimb plexus, some of them regenerated into limb nerves that lay outside the axons' normal segmental boundaries, and many regenerated into the medial femoral cutaneous nerve, a pathway normally limited to sensory axons. These observations suggest that the ultimate destinations of regenerating axons are largely determined by structures the axons encounter as they penetrate the distal nerve stumps. Thus, axons regenerating from a severed VR grow into that root's own distal stump and reinnervate the hindlimb in a manner that is segmentally appropriate; axons transected near the plexus have access to the pathways of sensory, as well as motor, axons in all 3 lumbar segments, and establish innervation fields that are inappropriate for their segment of origin and their motor function.

The lh3 Glycosyltransferase Directs Target-Selective Peripheral Nerve Regeneration

“…We find that under these conditions axons retain a high degree of target specificity (80%), indicating a non-random mechanism of reinnervation, consistent with previous reports (Brushart, 1988; Grimm, 1971; Kuffler, 1986a; Lee and Farel, 1988; Mark, 1965; Sperry and Arora, 1965; Stephenson, 1979). We observed that regenerating axons initially extend highly dynamic growth cones randomly towards both correct and incorrect targets before selecting their appropriate path.…”

“…Moreover, misguided axons can innervate inappropriate targets, leading to involuntary muscle contractions such as those observed in facial palsy (Kimura et al, 1975; Spector et al, 1991). Several studies argue that this sparse and/or ectopic axonal reinnervation is the result of regenerating axons selecting their path at branch points in a stochastic manner (English, 2005; Scherer, 1986; Westerfield, 1987; Westerfield and Powell, 1983), while others conclude that regenerating axons somehow ‘recognize’ their original trajectory (Brushart, 1988; Grimm, 1971; Kuffler, 1986a; Lee and Farel, 1988; Mark, 1965; Sperry and Arora, 1965; Stephenson, 1979). However, the mechanisms and molecules that enable regenerating axons to select their original trajectory at branch choice points in vivo have remained elusive.…”

Expression of a Chemorepellent Factor, Slit2, in Peripheral Nerve Regeneration

“…The critical feature of crush injuries is that the continuity of basal lamina tubes is protected from injury; in contrast, that of transect/repair injuries is that continuity is completely disrupted. [6][7][8] We operated on the right sciatic nerve of adult male Wistar rats (180-250 g) under deep anesthesia with sodium pentobarbital (40 mg/kg, i.p.). In the transect/repair group (n ¼ 10), the nerve was transected with a fresh razor blade approximately 1 cm from the sciatic notch, and immediately repaired using 10-0 nylon sutures.…”

“…10) As long as the basal lamina tubes remain intact, they guide the regenerating axons to the original target. 6,7) Complete transection of the peripheral nerve under transect injury disrupts the continuity of the basal lamina tubes, resulting in potential misdirection of regenerating A, Electrophoresis of PCR products from normal and crushed sciatic nerve templates showed a single slit1, slit2, robo1, and robo2 band. B, Electrophoresis of PCR products from normal and transected/repaired sciatic nerve templates showed a single slit1, slit2, robo1, and robo2 band.…”

Accuracy of regenerating motor neurons: Influence of diffusion in denervated nerve

“…Both of these mechanisms could thus result in muscle-derived signals accumulating in specific Schwann cell tubes (Bands of Bungner) at the parent nerve repair site. The eventual distal destination of regenerating axons is largely determined by the Schwann cell tubes that they enter at the nerve transection site (Brown and Hopkins, 1981, Brown and Hardman, 1987, Lee and Farel, 1988, Nguyen et al, 2002). Functional recovery will therefore largely depend upon the accuracy of these initial choices.…”