DEVELOPMENT OF THE PRIMARY AFFERENT PROJECTION IN HUMAN SPINAL-CORD

The development of spinal cord circuitry in humans is poorly character ized, primarily because standard anatomical tracers must be actively t ransported, which requires living tissue. Intensely fluorescent lipid- soluble tracers have largely eliminated this problem, at least for cir cuits that can be traced over short distances. We have, therefore, use d the carbocyanine dye DiI (1,1-dioctadecyl-3,3,3,3-tetramethyl-ind pe rchlorate) to study the development of the dorsal root afferent projec tion to fetal human spinal cord between 8 and 19 weeks of gestation. W e show here that the dorsal root afferents enter the gray matter of th e spinal cord very early in gestation. By 8 weeks, a few axons have al ready reached the motor pools. These axons, presumably spindle afferen ts, traverse the length of the spinal gray matter in fascicles to reac h different groups of motor neurons. As development progresses, these axons project to the ventral horn and branch in a restricted area in t he intermediate zone as well as in the motor pools. Between 11 and 19 weeks of gestation, axons in the ventral horn elaborate boutons that a ppear to be in proximity to the motor neuron somata and their proximal dendrites. Other groups of axons penetrate the gray matter of the spi nal cord all along the mediolateral extent of the dorsal horn. These a xons descend to lamina IV, and then turn upward to terminate in lamina e III and IV, arborizing primarily rostrocaudally. The time course of the development of these axons parallels that of the axons projecting to the ventral horn. On the basis of their laminar termination and pat terns of distribution, we suggest that these are the central axons fro m dorsal root ganglion neurons that innervate low-threshold mechanorec eptors in the periphery. Axon arborizations in laminae I and II were s parse, even at the latest developmental stages examined. It is unclear whether their specific connections have not yet developed or whether DiI does not diffuse well along these small-caliber axons. This charac terization of the development of the laminar specific projections of d orsal root ganglion neurons provides a foundation for studies of the e xpression of genes that may be implicated in dorsal root axon growth a nd branching in humans. (C) 1995 Wiley-Liss, Inc.