The astroglial cell that guides nerve fibers from growth cone to synapse in organotypic cultures of the fetal mouse spinal cord.
We present electron microscopic and autoradiographic studies done using organotypic cultures of spinal cord explants excised from 15 days of gestation mouse embryos. Nerve fibers growing from the spinal cord explant carry at their tips immature mitotic astrocytic cells that lead their growth cones. These glial cells divide only during the active phase of neuronal growth, and correspond ultrastructurally to radial glia. They provide a specific cellular substrate for neuronal growth. Some growth cones form axoglial synapses with smooth membranes of immature glial cells. In contrast, maturing glial cells sprout cytoplasmic processes that tightly wrap individual growth cones and effectively arrest their growth. Next, the processes gather nerve endings into islets and nerve fibers into bundles. After internalizing nerve endings, the glial processes withdraw, bringing the endings into contact with each other. The direct neuronal appositions lead to the transformation of growth cones into presynaptic endings, signaled by their collection of presynaptic vesicles. Clustering of the vesicles at presynaptic axoglial or axodendritic membranes indicates the onset of synaptogenesis-completed by differentiation of spinous and compound synapses. Concomitant with the progress of synaptogenesis, astrocytic investment within the neuropil progressively diminishes. The differentiating astrocytic processes show secretory and tethering activity toward nerve fibers and their endings. Our observations demonstrate that astroglial cells-depending on their developmental stage-first promote and then arrest neuronal growth, and induce synaptogenesis. Thus, at any time, the growing nerve fibers are not only supported but also controlled by the astroglial cells.
Sobkowicz
Hanna M
HM
Department of Neurology and Medical School Electron Microscopy Facility, University of Wisconsin, Madison, WI 53706, USA. hmsobkow@facstaff.wisc.edu
Waclawik
Andrew J
AJ
August
Benjamin K
BK
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001345:Autoradiography; D002454:Cell Differentiation; D005333:Fetus; D020439:Growth Cones / Q000648:ultrastructure*; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D009412:Nerve Fibers / Q000648:ultrastructure*; D009924:Organ Culture Techniques; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development*; D013569:Synapses / Q000648:ultrastructure*