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Biomedical subjects

S Jhaveri

Publications and source records attributed to S Jhaveri.

At least 37 records · Page 2Linked to original sources
PubMed1996

Unilateral containment of retinal axons by tectal glia: a possible role for sulfated proteoglycans.

(1) A distinct group of radial glia resides along the roofplate of the mesencephalon. Results of experiments, in which the neonatal tectum is manipulated surgically, point to the involvement of these glia in compartmentalizing retinotectal axons to one side of the midbrain. (2) Immunohistochemical studies document that the GAGs CS and KS are expressed along these midline glia during development: their expression occurs after the intertectal axons grow across the midline, but is coincident with the time of ingrowth of retinotectal axons, which fail to cross the midline. Together with results of in vitro experiments from other laboratories, these observations suggest that CS and KS are involved in the barrier function of the midline cells. (3) Preliminary data on biochemical characterization of PGs in developing tectum indicate that similar PG core proteins are found in the midline region as well as in the lateral tectum, whereas metabolic labeling shows a significantly higher uptake of radioactive sulfates along the midline. Thus differential glycosylation of proteins along the midline is likely, along with the possibility that it is the sugar chains which contribute to the barrier function of the raphe glia. Taken in the context of what we currently know about the biochemical heterogeneity of PGs, their developmental expression, and their functions in relation to the growth of axons from a variety of different neuronal cell types, it is clear that the analyses of interactions between PGs and growing axons must occur at several different levels, not the least of which involves a detailed understanding of the milieu in vivo within which these interactions take place.

Animals↗
PubMed1995

Intrinsic changes in developing retinal neurons result in regenerative failure of their axons.

The failure of mature mammalian central nervous system axons to regenerate after transection is usually attributed to influences of the extraneuronal milieu. Using explant cocultures of retina and midbrain tectum from hamsters, we have found evidence that these influences account for failure of regrowth of only a small minority of retinal axons. For most of the axons, there is a programmed loss of ability to elongate in the central nervous system. We show that there is a precipitous decline in the ability of retinal axons to reinnervate tectal targets when the retina is derived from pups on or after postnatal day 2, even when the target is embryonic. By contrast, embryonic retinal axons can regrow into tectum of any age, overcoming growth-inhibiting influences of glial factors.

Age Factors↗
PubMed1995

Glial environment in the developing superior colliculus of hamsters in relation to the timing of retinal axon ingrowth.

We have examined the developmental changes of glial cell organization in the superior colliculus of embryonic and neonatal hamsters in reference to the known sequence of retinal axon ingrowth and arborization in the midbrain. Immunolocalization of vimentin, a marker for neuronal and glial cell precursors, reveals a uniform distribution of radially oriented cells, with perikarya located at the ventricular surface and thin, elongated processes fanning out toward the pia. These vimentin-positive cells, referred to as the lateral radial cells, are present in the tectum from embryonic day (E) 10 (earliest day examined) until approximately postnatal day (P) 5. Vimentin expression in the lateral radial cells decreases markedly during the second week of postnatal life: application of DiI to the ventricular surface reveals that the pial attachment of the lateral radial cells is withdrawn and that the radial processes are gradually pulled back toward the ventricular zone. By P14, virtually no vimentin-positive radial cells are detectable in the superior colliculus. At no time during development are the lateral radial cells immunopositive for the glial fibrillary acidic protein (GFAP); however, shorter, vimentin-positive astrocytic profiles can be seen in the tectum around the time the radial fibers have been withdrawn, suggesting that at least some radial cells are transformed into astrocytes that will colonize the mature colliculus. At approximately E12, a second group of cells, referred to as the midline radial glia, is detected at the tectal midline. These cells are tightly bundled, forming a raphe in the tectum. They are intensely vimentin positive from E13 until at least P14. From the time of birth, the midline radial cells also exhibit intense immunoreactivity for GFAP. The lateral radial cells are present in the superior colliculus prior to and during the period of neurogenesis but remain well past the time when collicular neuronal migration is completed. Pial processes of the lateral radial cells are present within the superficial tectal layers during the time retinal axons are entering this target; they may be involved in directing the growth and initial collateralization of retinotectal axons. Their withdrawal from retinorecipient collicular zones begins at about the time arbors are being elaborated on retinal axons. In contrast, the midline glia become distinct just prior to the time retinal axons enter the superior colliculus and persist during the time retinotectal projections are being fully established. These raphe glia may be involved in maintaining the laterality of the retinotectal projection.

Animals↗
PubMed1995

Target influences on the morphology of trigeminal axons.

Axons grow in two stages: First, they exhibit rapid, target-directed extension; then they begin to collateralize and elaborate terminal arbors in their targets. To investigate possible regulatory influences on these phases of axon growth, we have used an in vitro paradigm in which we cocultured embryonic or postnatal rat trigeminal ganglion explants with isochronic, heterochronic, and/or heterotypic targets. Cultures were fixed after 5 days and ganglion cell processes were labeled with DiI. Trigeminal processes were able to regenerate into several peripheral targets as well as into CNS explants from trigeminal or nontrigeminal regions of the brain. In peripheral tissues, the processes showed target-specific growth patterns. In CNS tissue, the type of growth (unbranched extension versus collateralization/arbor formation) varied markedly with the explant age: If trigeminal ganglia were harvested at a time (E15) when their axons would be elongating in the embryo and cocultured with isochronic tissues, their processes had a simple morphology, were loosely bundled, and reconstituted a distinct fiber tract, mimicking their in vivo growth pattern. If, challenged by more mature tissue, axons of E15 ganglion cells formed discrete arbors. Finally, if trigeminal ganglia were harvested at an age (E20, PND 5) when their axons had already formed arbors in the brain and induced to innervate younger (E15) targets, their axons reverted back to the elongation stage. These results demonstrate that the target environment sets specific, developmentally regulated constraints on the patterns of growth manifested by primary sensory axons.

Animals↗
PubMed1994

Morphological specification of trigeminal neurites depends on target fields.

Primary sensory neurons bridge the sensory periphery to the central nervous system (CNS) via their two axonal processes. The morphological patterning of the terminals of each process in its respective target is unique. Whether the differences between peripheral and central axons result from an intrinsic developmental program of the ganglion cell body, or from target-derived signals is not known. To explore this issue, we have used an explant coculture system in which embryonic (E15) trigeminal ganglion explants were placed between a vibrissa pad and a brainstem explant, but the explants were rotated 180 degrees relative to their normal orientation. In other experiments, individual ganglia were placed between two vibrissa pad explants or between two slices taken through the brainstem. The cultures were fixed after several days and ganglion cell processes were labeled with the lipophilic tracer DiI. Results of the ganglion rotation experiments suggest that trigeminal axons which would be directed centrally in vivo can regenerate into peripheral targets, and peripheral axons can grow into CNS tissue. Similarly, in cocultures with two peripheral or two central targets, both processes of trigeminal ganglion cells can simultaneously invade vibrissa pad explants or project into brainstem slices. Moreover, in all cocultures the differentiation of each set of processes is specific to the target innervated by it. These results show that the axons of embryonic sensory neurons are not selective in their choice of targets, and that their morphological patterning is dictated by target-derived signals.

Animals↗
PubMed1994

Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice.

Sensory pathways of the brain generally develop from crudely wired networks to precisely organized systems. Several studies have implicated neural activity-dependent mechanisms, including N-methyl-D-aspartate (NMDA) receptors, in this refinement process. We applied the gene targeting to the NMDAR1 gene and created a mutant mouse that lacks functional NMDA receptors. The development of whisker-related patterns in the trigeminal nuclei of the mutant mice and their normal littermates was compared. We show that in the mutant mice pathfinding, initial targeting, and crude topographic projection of trigeminal axons in the brainstem are unaffected, but that whisker-specific patches fail to form. Our results provide a direct demonstration of the involvement of the NMDA receptor in the formation of periphery-related neural patterns in the mammalian brain.

Animals↗
PubMed1993

Target-derived influences on axon growth modes in cultures of trigeminal neurons.

Cellular and molecular signals involved in axon elongation versus collateral and arbor formation may be intrinsic to developing neurons, or they may derive from targets. To identify signals regulating axon growth modes, we have developed a culture system in which trigeminal ganglion cells are challenged by various target tissues. Embryonic day 15 (E15) rat trigeminal ganglion explants were placed between peripheral (vibrissa pad) and central nervous system targets. Normally, bipolar trigeminal ganglion cells extend one process to the vibrissa pad and another to the brainstem trigeminal complex. Under coculture conditions, the peripheral processes invade the vibrissa pad explants and form a characteristic circumfollicular pattern. Central processes of E15 ganglion cells invade many, but not all, central nervous system tissues. In isochronic (E15) central nervous system explants such as brainstem, olfactory bulb, or neocortex, these central processes elongate and form a "tract" but have virtually no arbors. However, in more mature targets (e.g., a section from postnatal brainstem or neocortex), they form arbors instead of a tract. We conclude from these observations that whether trigeminal axons elongate to form a tract, or whether they begin to arborize, is dictated by the target tissue and not by an intrinsic developmental program of the ganglion cell body. The explant coculture system is an excellent model for analysis of the molecular basis of neuron-target interactions.

Animals↗
PubMed1993

Midline glia of the tectum: a barrier for developing retinal axons.

A specialized group of radial glial cells constitutes a dorsal raphe in the mesencephalon and serves, at least, in part, to maintain the laterality of the retinotectal projection during development. Disruption of these cells is necessary, but may not be sufficient, for overriding their barrier function. Sulfated proteoglycans localized at the tectal midline form a putative molecular basis for the blockade; however, this blockade is selective: other fiber systems, such as the intertectal axons and under certain conditions the corticotectal axons, can cross the midline. Experimental studies of the tectal midline cells are advancing our understanding of the nature of boundaries in the developing brain.

Animals↗
PubMed1992

Myelination of the cerebral commissures of the hamster, as revealed by a monoclonal antibody specific for oligodendrocytes.

Myelination of the cerebral commissures of the hamster was studied by immunostaining with a monoclonal antibody (Rip) specific for oligodendrocytes. Immunostained, preensheathing cells were first observed in the anterior commissure on P6 (P1 = day of birth). By P8, immunopositive oligodendrocytes and myelinated fibers clustered around some of them were detected within the posterior limb of the anterior commissure, ventrally at the rostral half of the callosum, and in the hippocampal commissure. On P12, all the commissures had myelinated fibers throughout their extent, but the callosum and the hippocampal commissure exhibited higher densities of myelinated fibers rostrally. Between P15 and P22, the pattern of myelination approached that of the adult. In the context of other developmental events, myelination of the corpus callosum and of the anterior commissure is a late event, occurring predominantly after stabilization of axon number, either at the end of the progressive accretion of axons, as in the anterior commissure, or after the selective elimination of callosal projections.

Animals↗
PubMed1992

Oligodendrocytes and myelin formation along the optic tract of the developing hamster: an immunohistochemical study using the Rip antibody.

The monoclonal antibody Rip recognizes an antigen specific to oligodendrocytes and their processes (Friedman et al: Glia 2:380, 1989). We have used this antibody to document the appearance of oligodendrocytes and the sequence of ensheathment of axons along the optic tract (OT) and within its major target areas in neonatal (P3-P21) and adult hamsters. Myelination of axons in the visual pathway follows an overall proximo-distal gradient. On P3, immunopositive, pre-ensheathing oligodendrocytes are detected in the OT ventral to the lateral geniculate body (LGB) whereas myelin segments are present around OT axons by P5. The first pre-ensheathing oligodendrocytes are detected medially in the LGB on P7 and myelinated axons in the overlying OT by P11. In the superior colliculus, pre-ensheathing oligodendrocytes are present in the optic fiber layer (SO) on P7, but not in the superficial gray layer (SGS) until P11. Myelination of axons within SO proceeds along a marked rostro-caudal gradient. On P14, axons in rostral SO are heavily myelinated; thereafter, ensheathment continues caudally within the SO and the SGS. The progressive invasion of oligodendrocytes along the proximo-distal axis of the optic pathway, and the corresponding myelination of OT axons, are discussed in the context of a possible inhibitory role of oligodendrocytes in regulating the regenerative propensity of retinotectal axons.

Animals↗
PubMed1992

Trigeminal ganglion cell processes are spatially ordered prior to the differentiation of the vibrissa pad.

The rodent trigeminal system is characterized by the punctate organization of its afferents and neurons that replicate the distribution of mystacial vibrissae and sinus hairs on the snout. We have examined the development of topographic equivalence between the sensory periphery on the snout and the brainstem trigeminal nuclei in rats. Lipophilic tracers Dil (1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) and DiA [4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide] were used to label trigeminal ganglion cells and their processes differentially from discrete regions of the presumptive vibrissa field in fixed embryos. Our results show that trigeminal ganglion cell processes are spatially ordered as they reach their peripheral and central targets on embryonic day 12 (E12). Peripheral processes of dorsomedially situated ganglion cells course dorsally toward the presumptive vibrissa field, and those of ventrolaterally situated ganglion cells project ventrally. On E13, the central processes of dorsomedially situated ganglion cells enter the brainstem medially whereas those of ventrolaterally situated ganglion cells enter laterally. This spatial order of trigeminal ganglion cell processes precedes the emergence of vibrissa rows in the periphery and the differentiation of brainstem trigeminal nuclei. Thus, the subsequent transfer of the vibrissa-related pattern to the brainstem trigeminal nuclei occurs along a preexisting, spatially aligned bridge formed by the trigeminal ganglion cells.

Animals↗
PubMed1991

Barrel construction in rodent neocortex: role of thalamic afferents versus extracellular matrix molecules.

The rodent primary somatosensory cortex is characterized by aggregates of cellular and axonal elements that replicate the distribution of mystacial vibrissae on the face. The periphery-related cortical pattern ("barrels") is influenced by an amalgam of elements extrinsic (i.e., afferents) and intrinsic (i.e., neurons, glia, and their substrate) to the developing neocortex. To assign the role of some of these elements in cortical pattern formation, we have examined the temporal correlation between periphery-related patterns formed by thalamocortical axons and by extracellular matrix (ECM) molecules associated with neurons and glia in the cortex. Thalamocortical axons were labeled with the lipophilic tracer 1,1'-dioctydecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in aldehyde-fixed neonatal rat brains, and the same brains were also prepared for immunohistochemical localization of ECM molecules cytotactin and cytotactin-binding proteoglycan. We present evidence that thalamocortical axons form a periphery-related pattern well before such an organization is detectable in the distribution of ECM molecules. Furthermore, a patterned distribution of ECM molecules results from the down-regulation of these molecules from barrel centers, where thalamic axons have established vibrissa-specific patches. We conclude that thalamic axons convey the blueprint of the sensory periphery onto the neocortex and that ECM molecules do not participate in the initial formation of this pattern.

Afferent Pathways↗
PubMed1991

Initial stages of retinofugal axon development in the hamster: evidence for two distinct modes of growth.

In order to characterize differences in growth patterns of axons as they elongate toward their targets and during the initial stages of terminal arbor formation within the targets, we examined the primary visual system of fetal and newborn hamsters using three morphological methods: the Cajal-deCastro reduced silver method, the rapid Golgi technique, and anterograde transport of HRP. Axons emerge from the retina between the 10th and 11th embryonic days (E10-E11). The front of retinal axons crosses the chiasm, extends over the primitive dorsal nucleus of the lateral geniculate body (LGBd) by E13, and advances to the back of the superior colliculus (SC) by E13.5-E14. The rate of axon growth during this advance is nearly 2 mm/day. Collateral sprouts appear on axons around E15.5. In the LGBd and SC, these sprouts arise from multiple sites along the parent axons. Only one or a few of the sprouts continue to grow and branch, while others are eliminated. The net rate of axon collateral advance in this second phase is an order of magnitude slower than during the stage of axon elongation. Thus, formation of CNS projections may involve two qualitatively distinct modes of axon growth. The arborization mode contrasts with the elongation mode by the presence of branching, a lack of fasciculation and a slower average rate of extension. The stereotypic direct advance of axons during elongation also differs from the remodelling which occurs during arborization. The delay between axon arrival at targets and onset of arborization could be a reflection of axons "waiting" for a maturational change to occur in the retina or in targets. Arborization in the LGBd and SC is initiated around the same time, implicating the former possibility. However, a slower differentiation of retinal arbors in the SC, in addition to morphological differences of arbors in the two structures, suggests that alterations in substrate factors also play a critical role in triggering the early stages of arbor formation.

Aging↗
PubMed1990

Thalamic axons confer a blueprint of the sensory periphery onto the developing rat somatosensory cortex.

In order to study the role of afferents in the maturation of cortical axons projecting from the ventrobasal thalamic complex (VB) to the barrel field (SI) cortex were labeled with the carbocyanine dye DiI, in aldehyde-fixed embryonic and newborn rat brains. Our results reveal that the first few thalamic axons are in the cortical plate by embryonic day (E) 19. Between E19 and the day of birth (E21 = PND 0), layers V and VI differentiate from the lower part of the cortical plate. On PND 0, a plexus of growth-cone tipped thalamic axons is present within the cortical plate and a few VB fibers have reached the marginal zone. Increasing numbers of thalamic afferents invade and ramify within the cortical plate on PND 1 and, over the course of the next 24 h, form a vibrissa-specific pattern in the lower part of this zone, prior to the differentiation of layer IV into a distinct lamina. This periphery-related organization is exhibited by VB afferents earlier than reported for other afferents to the cortex, by glia- or neuron-associated extracellular elements or by the cytoarchitectonic specializations (barrels) of stellate cells. Our observations, in conjunction with the previous studies, demonstrate that thalamic afferents may have a pivotal role in determining the morphological specification of the primary somatosensory cortex.

Aging↗
PubMed1990

Maturation of projections from occipital cortex to the ventrolateral geniculate and superior colliculus in postnatal hamsters.

The development of corticofugal axons from the posterior cortex of young (ages P3-P11, P15 and P22) and adult Syrian hamsters was investigated by anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). On P3 and P4, 30 h after tracer was deposited in the cortex, The HRP reaction product was observed in the dorsal nucleus of the lateral geniculate body and in the lateral posterior nucleus of the thalamus, but no labeled axons were observed in the ventral nucleus of the lateral geniculate body (LGBv) until P5. Axon arborization, indicated by a granular precipitate scattered throughout the LGBv was light on P6 and robust on P7. Adult-like patterns of cortico-LGBv innervation were present by P11. The time course for the development of corticotectal fibers was similar to that for the cortico-LGBv projection: labeled cortical efferents were present in the pretectum on P5, but these did not enter the optic fiber layer of the superior colliculus (SC) until the following day (P6). Substantial invasion of the superficial gray layer, resulting from possible arborization of cortical axons in the optic fiber layer, occurred on P9. An adult-like distribution was evident by P11. Thus, corticofugal efferents to the LGBv and to the SC follow a similar developmental sequence, with the LGBv afferents maturing slightly earlier. There appears to be, however, a significant difference in the 'waiting periods' for the two systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗