Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target.

As axons grow past intermediate targets, they change their responsiveness to guidance cues. Local upregulation of receptor expression is involved, but the mechanisms for this are not clear. Here protein synthesis is traced within individual axons by introducing RNAs encoding visualizable reporters.

Reduced tumorigenicity of rat glioma cells in the brain when mediated by hygromycin phosphotransferase.

Object: A variant of C6 glioma cells, C6R-G/H cells express hygromycin phosphotransferase (HPT) and appear to have reduced tumorigenicity in the embryonic brain. The goal of this study was to investigate their reduced capacity to generate tumors in the adult rat brain.

Methods: Cell lines were implanted into rat brains and tumorigenesis was evaluated.

Generation of a radial-like glial cell line.

Rat C6 glioma is a cell line that has been used extensively as a model of astroglia. Although this cell line retains many of the properties of developing glia, it does not resemble morphologically the specialized form of glia found embryonically, the radial glia. In experiments designed to study a mutant form of receptor protein tyrosine phosphatase beta, we isolated a subclone of C6 called C6-R which, like radial glia, assumes a highly polarized radial-like morphology in culture.

Fibroblast Growth Factor Receptor Function Is Required for the Orderly Projection of Ganglion Cell Axons in the Developing Mammalian Retina.

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin.

Fibroblast growth factor receptor function is required for the orderly projection of ganglion cell axons in the developing mammalian retina.

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin.

Unique changes of ganglion cell growth cone behavior following cell adhesion molecule perturbations: a time-lapse study of the living retina.

In the mammalian retina, multiple mechanisms are responsible for guiding retinal ganglion cell axons to the optic fissure. In the present study we have used time-lapse videomicroscopy to show that, within the center of the retinal neuroepithelium, growth cones use a scaffold of previously formed axons as a substrate for guidance. High magnification time-lapse videomicroscopy of normal growth cones in the midretina have shown that they have the ability to alter their shape from long, streamlined forms that hug other axons to more flattened forms that move between axons or neuroepithelial endfeet.

Multiple factors govern intraretinal axon guidance: a time-lapse study.

In this study, the multiple factors that govern the unidirectional path of intraretinal axons, as well as the cellular movements prior to and during early axonogenesis, were investigated using time-lapse videomicroscopy. For several hours prior to overt axon elongation, young retinal ganglion cells send out transient minor processes in all directions at the pial surface. Time-lapse analysis of the chondroitin sulfate (CS)-containing matrix that has been suggested to play an important role in regulating this early differentiative event revealed the dynamic, wavelike properties of this extracellular matrix component.

The earliest patterns of neuronal differentiation and migration in the mammalian central nervous system.

With the use of four independent cell markers and Brd-U birthdating we have charted the earliest stages of neuronal differentiation and migration in the developing rat central nervous system, including the cortex, spinal cord, and retina. One of the markers, the monoclonal antibody 2G12, labeled a large subpopulation of differentiating cells that uniformly lined the ventricles throughout these CNS regions at unexpectedly early ages. Immunocytochemistry demonstrated that, in cortex, the 2G12 antigen could appear in cells during mitosis.

Exogenous glycosaminoglycans induce complete inversion of retinal ganglion cell bodies and their axons within the retinal neuroepithelium.

Prior to forming an axon, retinal ganglion cells retain a primitive radial configuration while maintaining ventricular and vitreal endfeet attachments. During their subsequent differentiation, ganglion cells polarize their cell body and axon only along the vitreal surface. When the ventricular surfaces of intact retinas in organ culture were exposed to free chondroitin sulfate (CS) in solution, both the cell body and nerve fiber layers were repolarized to the opposite side of the neuroepithelium.

Chondroitin sulfate as a regulator of neuronal patterning in the retina.

Highly sulfated proteoglycans are correlated with axon boundaries in the developing central nervous system which suggests that these molecules affect neural pattern formation. In the developing mammalian retina, gradual regression of chondroitin sulfate may help control the onset of ganglion cell differentiation and initial direction of their axons. Changes induced by the removal of chondroitin sulfate from intact retinas in culture confirm the function of chondroitin sulfate in retinal histogenesis.