Neurotropic influence of mesenchymal limb target tissue on spinal cord neurite growth in vitro

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Abstract
Peripheral nerve fiber outgrowth from developing spinal cord is proposed to be under the influence of the limb bud target which, at the time of nerve fiber invasion, is in an essentially premuscular, mesenchymal condition. Thus, the true target for elongating spinal nerve fibers in early development is mesenchyme rather than differentiated skeletal muscle. Spinal cord explants derived from stage V larval Rana pipiens were cultured in a defined medium in the presence or absence of mesenchymal limb tissue or limbconditioned medium (LCM). Analysis of quantified neuritic outgrowth under these conditions demonstrated a dependency on the target tissue for enhanced nerve fiber density and oriented growth. The characteristics of neuritic growth in the presence of limb mesenchyme or LCM changed from the relatively sparse and straight outgrowth of control cords to dense, wavy arborizations. Areas of the cord explants nearest the limb tissue exhibited the greatest increases in nerve fiber density and morphologic complexity. Additionally, an inverse relationship existed between growth enhancement and the cord-to-target distance. Regulation of directed nerve growth in vitro is suggested to result from a diffusible, target-originated growth factor that binds to the attachment substratum as a concentration gradient guidance pathway with implications for mechanisms of in vivo nerve growth.