Target control of neuronal development during formation of the spinal reflex arc: An operant model

Abstract

The effects of target tissues on the neural centers of the developing spinal reflex arc of frog tadpoles have been integrated to form a model explaining the spatial and temporal interactions of neuron and target. Spinal cord responds to appropriate targets earlier than does sensory ganglion in tissue culture. Neuronal growth and survival responses to target tissues in vitro may explain the regulation of development in situ.Key words: nerve growth, neuron survival, neuron maturation, nerve-target, spinal arc INTRODUCTIONRegulation of neuronal growth and survival by target tissues has been demonstrated for several neural systems in vitro [Varon and Adler, 19811. As part of normal developmental processes, neuronal death has been demonstrated frequently and appears to be related to events at the innervation target in situ [Oppenheim, 1981; Cunningham, 19821. Similar involvement of targets in the directed growth of nerve fibers has been suggested from studies in which limb buds were transplanted to ectopic positions on the embryo [Hamburger, 1939; Lance-Jones and Landmesser, 19811. In general, some of the best clues as to the cellular mechanisms controlling the growth and survival (failure to die during the phase of normal neuronal death) have come from cell and tissue culture investigations. In addition to roles for neuronal targets, the importance of the substratum to which neurons attach and along which nerve fibers extend has been increasingly considered as a critical factor in understanding the controls for nerve growth and survival [Letourneau, 1975;Collins, 1980;Hawrot, 1980;Carbonetto et al, 1982; Schubert and La Corbiere, 19821. Our attention has focused on the tropic and trophic influences exerted by target tissues on the components of the developing spinal reflex arc with a concern directed to how these influences may be mediated by the substratum. Received June 25, 1982; accepted July 17, 1982. 0360-4012182/0802-03-0343$04.00 C \ 1982 Alan R. Liss, Inc. 344Pollack and Muhlach paradigms of tissues derived from the spinal cord, dorsal root ganglion (DRG) and hindlimb of the frog tadpole (Rana pipiens) have provided much of the evidence that a temporal dependence is superimposed on the actions of targets in eliciting nerve growth and survival [Pollack and Liebig, 1977;Pollack et al, 1979;Pollack et al, 1980; Pollack and Muhlach, 19811. Drawing upon the results of recent experiments carried out in our laboratory, together with some newly attained information regarding substratum influences and biochemical indices of neural maturation, we have formulated a model to explain the timed action of targets on the growth and survival of neural centers related to the formation of the reflex arc.It has become apparent that the controls for directing nerve growth from a center to a distant target reside in 1) the action of the target during a defined time period of development, 2) the limited time for response by the neuron, and 3) the growth substratum or extraneuronal environment. Similar controls appear to be in...

Stage‐dependent spontaneous frog dorsal root ganglion neuritogenesis on polylysine in vitro

“…Other than developmental stage dependency, there appeared to be no hinderance in neurite extension under the conditions of this culture system. The fact that the stage XI DRG produced the densest neuritic networks coincides with other findings from our laboratory (Pollack and Muhlach, 1982), indicating that, a t least on collagen, the DRG is most responsive to the presence of its target tissues, i.e., the limb or spinal cord, a t stage XI, a time when target Fig. 3.…”

Growth patterns of primary cultures dissociated from 3‐day‐old chick embryos: Morphological and biochemical comparisons

“…We further propose that the neurite-cell contacts may play a trophic role for neuronal differentiation. The flat cells innervated by neuritic extensions may release factors in the microenvironment ; neurite-promoting factors have been described to derive from glial cells, fibroblasts, and target cells such as muscle cells Collins, 1978;Dribin and Barrett, 1982;Manthorpe et al, 1980;Monard, 1973;Newgreen, 1984;Noble et al, 1984;Pollack and Muhlach, 1982;Varon and Adler, 19811. A rare but impressive growth pattern was the following: a long neurite extension began from a large aggregate, making contact with a smaller cluster of cells and appeared to be ensheathed (or be in contact) with a chain of spindle shaped cells. The possibility that this structure represents Schwann cells ensheathing neurite (axon?)…”

Development of presynaptic specializations induced by basic polypeptide‐coated latex beads in spinal cord cultures

“…Although the identities of the neurons in the explants are not known, Cohen and Weldon (1980) previously showed that when these explants were cocultured with Xenopus muscle cells, 70% of the contacts will induce the formation of ACh receptor clustering, a feature characteristic of motoneurons (Cohen and Weldon, 1980;Kidokoro et al, 1980). In explant cultures of larval Rana pipens spinal cord, neuritic outgrowth has been related to spinal motoneurons Pollack and Muhlach 1982). Furthermore, the specializations induced by the beads bear a striking resemblance to those seen at the NMJ.…”