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R Keynes

Publications and source records attributed to R Keynes.

15 recordsLinked to original sources

Peripheral, but not central, axotomy induces neuropilin-1 mRNA expression in adult large diameter primary sensory neurons.

Neuropilin-1 (NP-1) is a component of the receptor for semaphorin3a (Sema3a), a member of a large family of molecules with widespread expression and demonstrable influence (via their ability to repel growing axons) on nervous system development. Recent studies have shown that some types of adult mammalian neurons retain the capacity to respond to Sema3a, particularly in relation to neuronal injury and regeneration. Although variations in expression of Sema3a mRNA have been revealed in neurons in both the central and peripheral nervous systems in this context, relatively little is known about NP-1 expression patterns. In this study we investigated the expression of NP-1 mRNA in adult dorsal root ganglion (DRG) neurons in intact and lesioned animals. We compared the effect of unilateral lesioning of the sciatic nerve or unilateral dorsal rhizotomy at lumbar levels L4/5, and bilateral dorsal funiculus lesioning at thoracic levels T10/11 on NP-1 mRNA expression in the cell bodies of lumbar DRGs. A significantly increased level of NP-1 mRNA expression was detected only following sciatic nerve lesioning (P < 0.001), but not after rhizotomy or dorsal funiculus lesioning. Furthermore, this upregulation was mainly confined to large diameter neurons of DRGs at lumbar levels L4/5, which provide the main sensory contribution to the sciatic nerve. These results suggest a role for NP-1 in the axonal response to peripheral nerve injury, which may be specific to a particular subset of primary sensory neurons.

Age Factors↗

Evanescent science

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Journal Article↗

Axon guidance to and from choice points.

Significant progress has been made recently in understanding axon guidance to and from choice points. Netrins have been shown to function as conserved midline chemoattractants in vertebrates and insects, and receptors for netrins and semaphorins/collapsins have been identified. More evidence has accumulated that repulsion plays a key role in guidance, including the involvement of the ephrin/Eph receptor system in contact repulsion.

Animals↗

Surround repulsion of spinal sensory axons in higher vertebrate embryos.

We have tested whether the orientation of axons sprouting from bipolar dorsal root ganglion neurons is influenced by diffusible cues from surrounding tissues. Surface ectoderm, dermomyotome, and notochord exert strong chemorepulsion on axons growing in collagen gels, operating at separations beyond those found in vivo and active in cocultures of chick and mouse tissues. Basal and alar plates of the neural tube are devoid of activity, as is the posterior-half-sclerotome, which repels in a contact-dependent manner. When ganglia are sandwiched between dermomyotome and notochord placed at a distance, axon growth is channeled in a bipolar trajectory. These results show that gradients of diffusible repulsion molecules flanking axon pathways can generate linear patterns of axon growth. We suggest that such "surround repulsion" may function generally, in concert with contact-dependent guidance mechanisms, to guide axons in the developing nervous system.

Animals↗

Early phenotypic choices by neuronal precursors, revealed by clonal analysis of the chick embryo hindbrain.

The mechanisms that generate diverse neuronal phenotypes within the central nervous system are thought to involve local cues or cell-cell interactions acting late in neurogenesis, perhaps as late as the last precursor cell division. We describe here a clonal analysis of neuronal development in the chick hindbrain, using an intracellular tracer to mark single precursor cells, that suggests the operation of an alternative strategy. The majority of clones, ranging from 1 to 46 cells, contained neurons of only one of several possible phenotypes. These single-phenotype clones were not positionally restricted within a rhombomere but were interspersed with other clones containing distinct phenotypes. The assignment of neuronal phenotype in this brain region may, therefore, be made in early precursors and remembered through several rounds of mitotic expansion and dispersal.

Animals↗

Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions.

In the chick embryo hindbrain, morphological segmentation into rhombomeres is matched by metameric patterns of early neuronal differentiation and axonogenesis. Boundaries between rhombomeres coincide with boundaries of expression of murine regulatory genes. By clonal analysis using intracellular marking, we show here that the rhombomere boundaries are partitions across which cells do not move. When a parent cell is marked before the appearance of rhombomere boundaries, the resulting clone is able to spread into the neighbouring rhombomere. When marked after boundary appearance, the clone still expands freely within the rhombomere of origin, but it is now restricted at the boundaries. Rhombomeres in the chick embryo thus behave like polyclonal units, raising the possibility that they are analogous to the compartments of insects.

Animals↗

Segmentation and the development of the vertebrate nervous system.

1. Recent experiments on the development of neural segmentation in chick embryos are reviewed. 2. Segmentation of the spinal peripheral nerves is governed by a subdivision of the somite-derived sclerotome into anterior and posterior halves. Migrating neural crest cells and outgrowing motor axons are confined to the anterior sclerotome as a result, in part, of inhibitory interactions with posterior sclerotome cells. 3. The sclerotomal distribution of certain molecules known to influence growing nerve cells in vitro, namely laminin, fibronectin, N-CAM, N-Cadherin and J1/tenascin/cytotactin, suggest that these molecules play no critical role in determining the preference of nerve cells for anterior sclerotome. 4. Peanut agglutinin (PNA) recognises cell surface-associated components on posterior cells which, when incorporated into liposomes, cause the abrupt collapse of sensory growth cones in vitro. The PNA receptor(s) may be inhibitory for nerve cells in vivo. 5. The chick hindbrain epithelium is segmented early in its development. Each branchiomotor nucleus in the series of cranial nerves V, VII and IX derives from a pair of segments lying in register with an adjacent branchial arch. Neurogenesis of motor and reticular axons begins in alternate segments, suggesting parallels with insect pattern formation.

Animals↗

Segmental patterns of neuronal development in the chick hindbrain.

Identification of specific neuronal populations and their projections in the developing hindbrain reveals a segmental organization in which pairs of metameric epithelial units cooperate to generate the repeating sequence of cranial branchiomotor nerves. Neurogenesis also follows a two-segment repeat, suggesting parallels with insect pattern formation.

Animals↗

A fitness performance test for school children and its correlation with physical working capacity and maximal oxygen uptake.

The Canadian Association for Health, Physical Education and Recreation fitness test (CAHPER test) composed of six items was compared to two laboratory tests of endurance fitness, physical working capacity at a minute pulse rate of 170 (PWC(170)) and maximum oxygen uptake (Vo(2) max.) in over 500 Winnipeg school children of both sexes aged 6 to 17 years. CAHPER test results were similar to the national average published by CAHPER in a test booklet. Correlation coefficients (r) of Vo(2) max. for boys with the CAHPER tests were: sit-ups .42, broad jump .69, shuttle run .50, arm hang .43, 50-yard dash .60, 300-yard run .65; for girls the r values were about half the values for the boys. Much of the correlation between CAHPER tests and Vo(2) max. or PWC(170) depended on the association of each test with body size. When multiple correlations were obtained including surface area as the first variable, the only significant factor correlating with the endurance tests was the arm hang; none of the other tests showed a significant correlation. "Physical fitness" is task-specific, so that a subject's position in the scoring scale of a fitness test depends entirely upon the test. The CAHPER test for physical fitness shows little or no correlation with standard laboratory measures of endurance in average children.

Adolescent↗