The active migration of neurons from their sites of origin to their final destinations requires the unidirectional translocation of the nuclei and somatic cytoplasm within the growing leading processes. To explore the cellular machinery underlying this translocation, we determined the polarity of microtubules situated within the leading and trailing processes of migrating cerebellar granule cells in situ. Our analysis reveals that the newly assembled positive ends of the microtubules in the leading process uniformly face the growing tip, while their disintegrating negative ends face the nucleus. In the trailing process, by contrast, microtubule arrays are of mixed polarity. We suggest that the dynamics of slow polymerization in combination with fast disintegration of oriented microtubules create "push" and "pull" forces that contribute to the piston-like saltatory displacement of the nucleus and cytoplasm within the membrane cylinder of the leading process of the migrating neuron.The cerebellar granule cell has fascinated developmental neurobiologists since the classical description by Ramon y Cajal (1) of its orderly and sequential migration across the molecular layer of the cerebellar cortex. Migrating neurons initially extend a cell extension called the leading process, which is followed by the translocation of the cell's nucleus within the extended membrane envelope (2-4). Although many aspects of neuronal cell migration have been elucidated in recent years (reviewed in refs. 5-8), the molecular machinery that translocates the cell nucleus itself remains unknown. It seems reasonable that a considerable mechanical force including a rearrangement of cytoskeletal scaffolding is an essential prerequisite for this translocation since the entire cell body is propelled across the developing molecular layer, an area that is densely packed with the cellular processes of earlier-generated neurons. Electron microscopic analyses have revealed parallel arrays of microtubules in both the leading and trailing processes of granule cells as they begin to move across the molecular layer (2). The large number of microtubules and their longitudinal deployment in the leading process have implicated them in the translocation of a cell's soma (9, 10), but beyond this there is little known about how microtubule proteins become assembled and how they function in migrating neurons. Therefore, knowledge about the polarity of the assemblies, sites of nucleation and posttranslational modifications of microtubule components in the cytoplasm of premigratory granule cells may provide new insights into the mechanism of the movement of cells during their migration.Microtubules in mammalian neurons consist of a and f3 tubulin molecules polymerized in the form of a hollow tube (13). In general, new tubulin oligomeres are added to each microtubule at one pole, the positive end, and are deleted at the other pole, the negative end (14). The recently developed "hook assay" technique has permitted determination of the polarity of polymeriza...
Disappearance of fluorid-resistant acid phosphatase activity from the ipsilateral Rolando substance after transection of the peripheral nerve, is shown to be due to the cessation of enzyme supply from dorsal root ganglion cells to their central terminals. This is accompanied by (or ensues in consequence of) a fine structural derangement of these terminals ("degenerative atrophy"). Fine structural alterations of axon terminals undergoing degenerative atrophy, though similar to some extent to those seen during early phases of a Wallerian degeneration, are markedly different. Also myelinated nerve fibers, both in the dorsal horn and in dorsal columns, are affected by degenerative atrophy. This important, new trophical feature of sensory ganglion cells suggests a delicate metabolic balance between peripheral and central axonal branches of bipolar (pseudounipolar) cells. Degenerative atrophy raises serious implications in evaluating hodological experiments based upon Wallerian degeneration and offers new perspectives for theoretical and clinical neurology.
Thiamine monophosphatase (TMPase) has been selectively localized in small dorsal root ganglion cells and in their central and peripheral terminals. Light microscopic localization of TMPase, and its alterations due to transganglionic effects, are identical with those of fluoride-resistant acid phosphatase (FRAP), but are not contaminated by the ubiquitous lysosomal reaction inevitable in trivial acid phosphatase-stained sections. TMPase is inhibited by 0.1 mM NaF, which is slightly less than the concentration needed to inhibit FRAP (0.2-0.4 mM). It is assumed that TMPase and FRAP are identical enzymes. In the perikaryon of small dorsal root ganglion cells, TMPase is located in the cisterns of the endoplasmic reticulum and in the Golgi apparatus. The central terminals of these cells are scalloped (sinusoid) axon terminals, surrounded by membrane-bound TMPase activity. Central terminals outline substantia gelatinosa Rolandi throughout the spinal cord, as well as the analogous nucleus spinalis trigemini in the medulla. TMPase-active central terminals outline "faisceau de la corne postérieure" in the sacral cord, as well as Lissauer's tract in the thoracic, upper lumbar, and sacral segments, and the paratrigeminal nucleus and the terminal (sensory) nucleus of the ala cinerea in the brainstem. Peripheral terminals displaying TMPase activity are fine nerve plexuses of C fibers. The TMPase activity of the central terminals disappears after dorsal rhizotomy in the course of Wallerian degeneration, and is depleted in the course of transganglionic degenerative atrophy (after transection of the related peripheral sensory nerve). TMPase is an outstanding genuine marker for the study of transganglionic regulation in Muridae.
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