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C A Mason

Publications and source records attributed to C A Mason.

At least 73 records · Page 4Linked to original sources

Mechanisms of glial-guided neuronal migration in vitro and in vivo.

Our laboratory has developed an in vitro model system in which glial-guided neuronal migration can be observed in real time. Cerebellar granule neurons migrate on astroglial fibers by apposing their cell soma against the glial arm, forming a specialized migration junction, and extending a motile leading process in the direction of migration. In vitro assays indicate that the neuronal antigen astrotactin functions as a neuron-glia ligand, and is likely to play a role in the movement of neurons along glial fibers. In heterotypic recombinations of neurons and glia from mouse cerebellum and rat hippocampus, neurons migrate on heterotypic glial processes with a cytology, speed and mode of movement identical to that of neuronal migration on homotypic glial fibers, suggesting that glial fibers provide a permissive pathway for neuronal migration in developing brain. In vivo analyses of developing cerebellum demonstrate a close coordination of afferent axon ingrowth relative to target cell migration. These studies indicate that climbing fibers contact immature Purkinje neurons during the migration and settling of Purkinje cells, implicating a role for afferents in the termination of migration.

Animals↗

Early climbing fiber interactions with Purkinje cells in the postnatal mouse cerebellum.

The time and place of initial contacts between afferent axons and their target cells are not known for most regions of the mammalian CNS. To address this issue, we have selectively visualized afferent climbing fiber axons together with their synaptic targets, Purkinje cells, in postnatal mouse cerebellum. Climbing fibers were orthogradely labeled by injection of rhodamine isothiocyanate into their brainstem source, the inferior olivary nucleus. Purkinje cells were localized with an antibody to a calcium-binding protein, calbindin D-28k (CaBP), in the same section or in adjacent sections. A novel view of the olivocerebellar projection and the morphology of climbing fiber arbors prior to the well-known "nest" stage has emerged from this analysis. At birth, climbing fibers project into the zone of Purkinje cells, before these cells have aligned into a monolayer. During this phase, climbing fibers have simple morphologies consisting of relatively unbranched terminal arbors and small tapered growing tips. Purkinje cells are arranged 3-6 cells deep and have tufted dendrites and relatively smooth somata. By postnatal days 3-4, climbing fibers branch over several adjacent Purkinje cell perikarya, which are still organized in a band several cells thick. From postnatal days 5-7, when climbing fibers subsequently make focused nests on individual cells, Purkinje somata are smoother and form a more distinct monolayer. Up to this time, however, climbing fibers continue to associate with Purkinje perikarya, even though Purkinje cell dendrites have emerged and branched extensively. By postnatal days 8-10, climbing fiber terminals climb onto the trunk of the relatively mature Purkinje dendritic tree. At birth, mossy fibers originating from the pontine nuclei resemble immature climbing fibers in that they also have a simple unbranched morphology and growing tips, but project only so far as the internal granule cell layer. Occasional individual fibers reach into the Purkinje zone both at postnatal day 0 and postnatal day 4, confirming that the fibers formerly described as "combination fibers" (Mason and Gregory, S4. J. Neurosci, 4:1715-1735) can be mossy in origin. These data demonstrate that climbing fibers project among Purkinje cells earlier than suspected, before these afferents begin to arborize and form pericellular nests. Our observations are not in accord with the view derived from autoradiographic tracing studies that as in other cortical areas, climbing afferents wait in the vicinity of Purkinje cells in the early neonatal period, then advance onto these cells in synchrony with Purkinje cell alignment into a monolayer and dendritic maturation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Some effects of growth conditions on steady state and heat shock induced htpG gene expression in continuous cultures of Escherichia coli.

Most of the data concerning heat shock gene expression reported in the literature are derived from batch culture experiments under substrate and nutrient sufficient conditions. Here, the effects of dilution rate and medium composition on the steady state and heat shock induced htpG gene expression have been investigated in continuous cultures of Escherichia coli, using a chromosomal htpG-lacZ gene fusion. During steady state growth temperature dependent patterns of the relative htpG expression were found to be largely similar, irrespective of the growth condition. However, nitrogen-limited growth resulted in a markedly reduced specific steady state htpG expression as compared to growth under carbon limitation or in complex medium, correlating qualitatively with the total cellular protein content. During heat shock, tight temperature controlled expression was evident. While the relative heat shock induced expression was largely identical at various dilution rates in a given growth medium, significantly different response patterns were observed in the three growth media at any given dilution rate. From these results a clearly temperature regulated htpG expression during both, steady and transient state growth in continuous culture is evident, which is further significantly affected by the growth condition used.

Culture Media↗

Retinal axon pathfinding in the optic chiasm: divergence of crossed and uncrossed fibers.

In the developing mammalian visual system, retinal fibers grow through the optic chiasm, where one population crosses to the opposite side of the brain and the other does not. Evidence from labeling growing retinal axons with the carbocyanine dye Dil in mouse embryos indicates that the two subpopulations diverge at a zone along the midline of the optic chiasm. At the border of this zone, crossed fibers grow directly across, whereas uncrossed fibers turn back, developing highly complex terminations with bifurcating and wide-ranging growth cones. When one eye is removed at early stages, uncrossed fibers from the remaining eye stall at the chiasm midline. These results suggest that crossed and uncrossed retinal fibers respond differently to cues along the midline of the chiasm and that the uncrossed fibers from one eye grow along crossed fibers from the other eye, both guidance mechanisms contributing to the establishment of the bilateral pattern of visual projections in mammalian brain.

Animals↗

Meander tail reveals a discrete developmental unit in the mouse cerebellum.

Analyses of phenotypic mutations with altered patterns of cellular organization in invertebrate systems have lead to the identification of genes important to histogenesis. Efforts to identify genes defining segments or compartments in mammalian systems and demonstrate a role for such genes in the establishment of the cellular architectonics of the brain have been hampered by the absence of phenotypic mutations that reveal compartments. Evidence is presented that in the cerebellum of the mutant mouse, meander tail, there is an abrupt transition from the normal cytoarchitecture seen in the posterior lobes to a severely disorganized cellular pattern. Thus, in the anterior lobes the Purkinje cells are positioned randomly throughout the cortex, and other cellular layers, including the internal granule cell layer, do not form. In addition, radial Bergmann glial processes are virtually absent. One explanation for the discrete boundary of the affected area in the anterior portion of this mutant cerebellar cortex is that the meander tail gene influences compartmental cellular organization in mammalian brain.

Animals↗

Activities of infection control practitioners during an outbreak of Salmonella typhimurium. Task Force of Association for Practitioners in Infection Control.

ICPs played an invaluable role, and their activities resulted in minimal nosocomial incidence. The survey reported two cases of nosocomial infection in patients, one in the medical service and one in the pediatric unit, as well as the reported employee cases. Two nosocomial employee cases were reported, a laboratory technologist and medical student. Implementation of these recommendations will make the job of the ICP easier during any outbreak. We believe that our interventions, interactions, and assistance positively affected the course of the epidemic. In the final analysis the activities of surveillance, supervision of isolation, education and consultation, employee health, and public relations served to strengthen the positive image of ICPs.

Allied Health Personnel↗

Childhood acute promyelocytic leukemia: a rare variant of nonlymphoid leukemia with distinctive clinical and biologic features.

Of 251 consecutive cases of childhood acute nonlymphocytic leukemia (ANLL) seen at St. Jude Children's Research Hospital over a 12-year period, 16 (6.4%) were classified as promyelocytic according to the French-American-British definition. Patients with this form of leukemia were older at diagnosis than the group representing all other ANLL subtypes (median age, 14.8 vs. 9.0 years); they had lower leukocyte counts (median, 4.5 vs. 25.9 x 10(9)/liter), and a higher percentage were girls (68% vs. 44%). They also were much more likely to have a coagulation abnormality (75% vs. 13%). Only 44% of the promyelocytic group achieved complete remission, compared with 79% of the remaining patients (p = 0.001); however, after a median follow-up of 3.5 years, all but two of the responding patients with promyelocytic leukemia remain in complete remission. The majority of induction failures in the promyelocytic group (six of nine) resulted from complications that developed during periods of marrow hypoplasia or before hypoplasia was induced; whereas in the comparison group, more than half of the patients who failed had evidence of absolute or relative drug resistance. It is concluded that acute promyelocytic leukemia in children differs sufficiently from other subtypes of childhood ANLL to justify clinical trials of selective therapy. Recommendations for the use of heparin and blood component support in these patients are given.

Adolescent↗

Acute nonlymphoblastic leukemia in infants: clinical presentation and outcome.

The presenting features and clinical outcome of acute nonlymphoblastic leukemia (ANLL) in infants and older children were compared to identify any differences that might suggest methods to improve therapy. Twelve of the 29 infants were boys and 17 were girls, with ages ranging from two days to 12 months (median, 7 months). By comparison with 222 patients greater than 1 year of age, infants were significantly more likely to have monoblastic or myelomonoblastic leukemia (P less than .0001), chloroma (P less than .0001), marked hepatomegaly (P = .001), and high leukocyte count (P = .005) and were less likely to have Auer rods (P less than .001). Each of these features except leukocyte count showed an association with infant ANLL in a multivariate analysis. Twenty-four (83%) of the infants attained a complete remission, a rate that was not significantly different from that of the older children. Even though infants had a significantly higher CNS relapse rate (P = .003), their event-free survival times were no different than those of older children (P = .74). Ten of the infants remain in initial complete remission for 5+ to 112+ months (median, 52+ months). Infants with ANLL did not have a poorer prognosis than older patients in our study; future protocols for this age group should emphasize more effective systemic therapy, preferably including an epipodophyllotoxin, as well as improved treatment for subclinical CNS leukemia.

Acute Disease↗

The extending astroglial process: development of glial cell shape, the growing tip, and interactions with neurons.

To analyze how astroglial cells attain the complex shapes that support neuronal migration and positioning in vitro (Hatten et al., 1984; Hatten 1985), early postnatal mouse cerebellar cells were plated in microcultures, and glial process outgrowth was monitored by high-resolution time-lapse video microscopy combined with immunocytochemical localization of antisera to glial filament protein (GFP), and by electron microscopy. The 2 principal astroglial forms seen in these cultures, stellate and Bergmann-like (Hatten et al., 1984), begin to develop their distinctive shapes by the outgrowth of processes in the first 8 hr after the cells are plated. Glial process extension is most vigorous in this period, resulting predominantly in stellate forms. A second population of glial cells, having fewer, longer processes reminiscent of Bergmann glia in vivo, first appears about 5 hr after plating. During the next 16-24 hr, while the stellate cells only slightly increase their process length, the bipolar cells double their length. The most striking feature of the elongating glial process is its highly motile tip, which rapidly extends microspikes and lamellopodia. Unlike the neuronal growth cone, which is the expanded terminal of a thin neurite shaft, the glial growing tip forms the end of a wide, paddle-like process that is filled with motile mitochondria and masses of glial filaments, and is bordered by an undulating lamella fringed by microspikes. Soon after the emergence of glial processes, cell-cell interactions between the growing glial process tip and granule neurons occur. Within minutes of an initial encounter between the glial process and the neuron, contact relationships that are stable during the observation period form between the cells. Subsequently, many neurons extend a small neurite onto the glial process, and astroglial process extension continues by the movement of the glial growing tip out beyond the neuron. Thus, cerebellar astroglia in vitro develop complex shapes in the same fashion as do neurons: the outgrowth of processes tipped by a motile ending. The growing tips of astroglial processes interact with neurons, resulting in the stable association of neurons and glia.

Animals↗

Cytology and neuron-glial apposition of migrating cerebellar granule cells in vitro.

In developing mammalian brain, many neurons migrate to their final position by moving in direct apposition to radially oriented glial cells. Glial-guided migration can be visualized in microcultures of mouse cerebellar cells by the combined use of cellular antigen markers and high resolution time-lapse video microscopy (Hatten et al., 1984; Edmondson and Hatten, 1987). Such studies have demonstrated the behavior of migrating cells and revealed a motile leading process on the migrating neuron that resembles an axonal growth cone and grows along extended glial fibers. To study the fine structural details of the migrating neuron and its neuron-glial apposition, we identified and monitored neurons in microcultures with video microscopy and examined the cytology and cellular contacts of the same cells with transmission electron microscopy. The cytology of the soma and leading process of migrating cells closely matches that described for granule cells in intact brain (Rakic, 1971). Newly observed structures include the presence of longitudinally oriented microtubules extending from a basal body in the soma into the leading process, and microfilament-rich filopodia arising from the soma and leading process. The most striking feature of actively migrating neurons is a specialized junction between the neuronal cell soma and apposing glial fibers. At this junction, here termed "interstitial density," the extracellular space is dilated to 20 nm and filamentous material in the intracellular cleft either spans the cleft or runs parallel to the cell membranes. Some interstitial fibrils are contiguous with, or are transmembranous extensions of, submembranous cytoskeletal elements that attach to microtubules. Interstitial junctions were not found between neurons that did not translocate in the observation period before fixation. Instead, stationary cells formed desmosomes (puncta and macula adhaerentia) at appositions with glial processes.

Animals↗

Glial filament protein expression in astroglia in the mouse visual pathway.

We have studied the onset of expression of glial filament protein (GFP) in astrocytes along a single axon trajectory, the mouse retinal axon pathway, and the relationship of GFP expression to maturation of astroglial morphology. In fetal optic nerve from embryonic day (E) 12 to E16, primitive glia (neuroepithelial cells) lack GFP, but express vimentin and contain intermediate filaments. GFP is expressed at E17 in two gradients: cells in the optic nerve become GFP-positive first in the borders of the nerve, then in the central nerve by postnatal day (P)0. The second gradient is a distoproximal one, with GFP appearing in the optic nerve at E17, in the optic chiasm by PO, and in the optic tract by P3. The expression of GFP in the optic nerve marks the transformation of radial neuroepithelial cells to multipolar astroglia, accomplished by outgrowth of filament-rich glial processes tipped by a growth cone. Several days after the onset of GFP expression in each portion of the pathway astrocytes exhibit a transient increase in staining, and resemble reactive astrocytes after injury. During this period, filaments are arranged in densely packed bundles, and appear coalesced at points. Thus, primitive glial cells in optic nerve express vimentin. In the retinofugal pathway, GFP is expressed in a distinct spatiotemporal sequence from optic nerve to optic tract. Finally, in contrast to neurons, the extension of astroglial processes is accompanied by the increased expression and assembly of intermediate filaments.

Aging↗

Septic shock.

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Child↗

Axon development in mouse cerebellum: embryonic axon forms and expression of synapsin I.

A fundamental question in central nervous system development is the timing of synaptogenesis in relation to invasion of targets by afferent axons. A related question is how growth cones transform into synaptic terminals. These two aspects of axon maturation were examined in developing mouse cerebellum, by labeling single axons with horseradish peroxidase, to study their form and cytology, and by immunocytochemical staining of a synaptic vesicle antigen, synapsin I, a phosphoprotein found on synaptic vesicles in all mature CNS synapses. From embryonic day 16 to postnatal day 3, horseradish peroxidase-labeled afferent axons extend well into the cerebellum and have simple forms. At embryonic day 16, axon growing tips are synapsin I-negative. Synapsin I is first expressed at embryonic day 17, and by embryonic day 18, fibers are stained throughout the cerebellum. Synapsin I expression coincides with a general increase in synaptic specializations, although growing tips continue to have the cytology of growth cones. During the period that axons have primitive shapes, synapsin I is distributed throughout the terminal arbor, corresponding to the presence of small vesicles along neurite lengths, even at non-synaptic sites. After postnatal day 3, when synaptic terminals develop into stereotypic shapes and engage in characteristic synaptic relations, synapsin I is restricted to boutons. Thus, the synapse-specific protein synapsin I is expressed in fetal mouse brain, long before nerve endings have the structure and connections of adult brain. In cerebellar axons, the expression of this protein follows axon arrival, coincides with the appearance of elementary synapses, and accompanies the transformation of growing tips into stereotypic synaptic boutons. The time course of expression of synapsin I, a phosphoprotein that may be involved in synaptic efficacy, suggests that transmitter release may influence early axon-target cell interactions.

Animals↗

Weaver mouse cerebellar granule neurons fail to migrate on wild-type astroglial processes in vitro.

To study the regulation of glial-guided neuronal migration, we have analyzed the behavior of cerebellar granule neurons purified from the homozygous weaver (wv/wv) B6CBA-w mouse, an autosomal recessive genetic mutation that suffers a failure of granule cell migration along Bergmann glial processes (Rakic and Sidman, 1973a, b; Rezai and Yoon, 1972), on the processes of astroglia purified from homozygous normal B6CBA-Aw-J-wv (+/+) mouse cerebella. When co-cultured with normal astroglia, weaver granule neurons failed to form neuron-glia contacts characteristic of migrating neurons and impaired normal astroglial morphological differentiation. Normal astroglial cells co-cultured with weaver granule cells had enlarged cell somata with stunted processes and enlarged endfeet compared to normal astroglia co-cultured with normal granule cells. In contrast, normal neurons associated with weaver astroglia, forming tight appositions seen for migrating neurons in vivo, and enhanced weaver astroglial morphological differentiation. Weaver astroglia co-cultured with normal granule cells contained a more normal complement of glial filaments and had a smaller perikaryon with longer, more tapered processes than their counterparts co-cultured with weaver neurons. These results suggest, in agreement with the study of Goldowitz and Mullen (1982) on heterozygous mutant chimeras, that the granule neuron is a primary site of action of the weaver gene, and further support our previous findings that neuron-glia interactions regulate astroglial morphological differentiation (Hatten, 1985).

Animal Population Groups↗

Growing tips of embryonic cerebellar axons in vivo.

Few studies have focused on the transformation of growth cones to mature synaptic arbors. To study these events in developing axons in vivo, we have labeled growing cerebellar axons with horseradish peroxidase (HRP) in postnatal stages [Mason and Gregory, 1984]. This report will provide the first data on embryonic cerebellar axons, and will ask whether growth cones differ in tracts and in target tissue and what features characterize axons that enter the cerebellum in fetal periods. During the earliest embryonic (E) periods examined (E16-19), axons in tracts have enlarged growth cones with lamellopodia and short filopodia that contain small and large vesicles. In contrast, axons within the cerebellar anlage from E16-postnatal day (P) 5 have fine calibers with a minimum of branching, and have small tapered growing tips. If synaptic contacts are made by such growing tips, there is little concomitant change in their shape. As target cells from layers and as their dendrites extend (P5-P7), growing tips and synaptic boutons differentiate according to the type of synaptic arrangement in which they engage. Enlarged, irregular expansions of growing tips correspond to synaptic contacts with multiple dendritic partners and are filled with large and small clear vesicles. Filopodia arising from such swellings, like the small undifferentiated growing tips of the type seen on embryonic axons, contain a mixture of vesicle types but make simple synapses with single profiles. Many axons make both kinds of synaptic structures, especially during the period when maturing axons give rise to long filopodia. Thus, growing tips have immature forms long after synaptogenesis begins, and use filopodial structures to elaborate synaptic arrangements. This analysis should elucidate the changes in growth cone form and cytology that reflect cell-cell interactions during synaptogenesis.

Animals↗

Development of cerebellar astroglia: transitions in form and cytoskeletal content.

The forms, disposition, and cytoskeletal contents of astroglia in immature mouse cerebellum were studied by immunocytochemical staining with antisera against two intermediate filament proteins, vimentin (Vim) (58,000 daltons) and glial filament protein (GF) (51,000 daltons). From embryonic (E) Day 15 to postnatal (P) Day 2, Vim is expressed in cells throughout the cerebellar anlage, including radial glia and Bergmann fibers, cells with amorphous shapes and 2-3 processes, and thick longitudinal elements oriented parallel to axons within axon tracts. GF is not expressed during the first few postnatal days, but by P7, there is a dramatic increase in GF-positive astrocyte-like cells in the putative white matter that are more densely stained and more crowded than at any other age. Between P7 and P14 all astrocytes throughout the cerebellum express both Vim and GF. From P21 on, Vim expression is progressively rarer in all astrocytes except for Bergmann fibers, and GF-positive astrocytes become less numerous. These findings raise two issues: (a) the lineage and relationships of cells expressing Vim and GF; (b) Since GF-positive cells appear as axon ingrowth ceases, axons must grow in a terrain comprised of glial cells that have a different cytoskeletal composition (vimentin), reflecting a less differentiated state, than mature astrocytes or than the GF-rich astrocytes that proliferate after injury in adult CNS.

Aging↗

Patterns of synaptic contact upon individually labeled large cells of the dorsal lateral geniculate nucleus of the cat.

Four large geniculate cells that were densely filled with horseradish peroxidase have been studied in detail, at first light microscopically, to define the shape and distribution of the dendritic arbors, and then electron microscopically, to define the pattern of synaptic contacts upon their surfaces. Three of the cells had the morphological characteristics of a class 1 cell, and one cell was intermediate between class 1 and 2. All of these cells had few of the characteristic grape-like appendages, thought to receive retinal input within synaptic glomeruli. Retinal afferents were mainly distributed around proximal juxtasomatic dendritic segments and dendritic branch points. Some retinal afferents made simple axodendritic contacts, while others formed a part of a synaptic glomerulus. None of the retinal afferents forming synapses near the perikaryon were involved in glomeruli. Within the glomeruli involving class 1 cells, retinal terminals can relate both to dendritic segments, particularly near branch points, as well as to dendritic appendages. The few singly placed grape-like appendages were always contacted by retinal afferents, but not necessarily in a glomerular arrangement. Terminals interpreted as cortico-geniculate were seen most commonly upon peripheral dendritic segments, while those containing pleomorphic vesicles (F) were distributed more or less evenly over all parts of the dendritic and perikaryal surface. The perikaryon itself was contacted by F-type terminals but was not contacted by retino-geniculate or cortico-geniculate terminals. A class of slender axonal terminal, containing round synaptic vesicles and few or no mitochondria, was found contacting two of the four perikarya, but the origin of these slender axons is unknown. It is concluded that the surfaces of geniculate class 1 cells can be separated into several functionally distinct zones on the basis of the synaptic contacts they receive.

Animals↗