Proliferation, Differentiation, and Survival of Rat Sensory Neuron Precursors in Vitro Require Specific Trophic Factors

Memberg, Stacey P.; Hall, Alison K.

doi:10.1006/mcne.1995.1025

Cited by 81 publications

(42 citation statements)

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“…Memberg and A. Hall, unpublished observations), and neurons in this population respond to NGF, NT3, and NT4 almost equivalently for short-term survival (Memberg and Hall, 1995). Thus, although functional subtypes in mature animals show significant neurotrophin specificity, the embryonic neurons used in the present experiments do not display those subtypes.…”

Section: Discussionmentioning

confidence: 58%

“…To test the possibility that DRG cells make NT3 in these cultures and that the NT3 can affect CGRP expression, anti-NT3 was added to E14.5 DRG neurons in the presence of NGF and serum. Many E14.5 DRG neurons can be supported in short-term assays by NT3 (Memberg and Hall, 1995), and that survival can be blocked with antibody to NT3 (Fig. 6 A).…”

Section: General Culture Conditions Did Not Regulate Cgrp Expressionmentioning

confidence: 96%

“…These data provide strong support that a subpopulation of DRG neurons can regulate CGRP expression in the absence of target tissues. E12.5 DRG neuron precursors are proliferative in vivo and in vitro (Lawson et al, 1974;Memberg and Hall, 1995), making direct quantitation difficult. In addition, although neurons at this age can be maintained easily in short-term cultures (Memberg and Hall, 1995), they can be difficult to support for long periods of time and thus were not used for subsequent studies.…”

Section: Cgrp Expression By Cultured Drg Neurons Was Temporally Similmentioning

confidence: 99%

“…E12.5 DRG neuron precursors are proliferative in vivo and in vitro (Lawson et al, 1974;Memberg and Hall, 1995), making direct quantitation difficult. In addition, although neurons at this age can be maintained easily in short-term cultures (Memberg and Hall, 1995), they can be difficult to support for long periods of time and thus were not used for subsequent studies. These results suggest that the initial expression and regulation of CGRP is an intrinsic property of some neurons and does not depend on an intact DRG or peripheral target contact.…”

Section: Cgrp Expression By Cultured Drg Neurons Was Temporally Similmentioning

confidence: 99%

“…At E14.5, NGF is a major short-term survival factor for rat DRG neurons, although at this stage NT3 and NT4 can also support similar populations of embryonic neurons for at least 2 d (Memberg and Hall, 1995). To test the possibility that neurotrophins affected long-term survival, neurons were counted by phase microscopy at 24 hr, 48 hr, and 10 d in vitro in NGF or a cocktail of NGF ϩ BDNF ϩ NT3.…”

Section: General Culture Conditions Did Not Regulate Cgrp Expressionmentioning

confidence: 99%

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The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

Hall

Hickman

et al. 1997

J. Neurosci.

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Adult sensory neurons differ chemically, morphologically, and functionally, but the factors that generate their diversity remain unclear. For example, neuropeptides are generally found in small neurons, whereas abundant neurofilament is common in large neurons. Neurons containing the neuropeptides calcitonin gene-related peptide (CGRP) or substance P were quantified using immunohistochemistry in rat lumbar dorsal root ganglion (DRG) at times before and after sensory neurons contact central and peripheral targets in vivo. No neurons in the newly formed DRG expressed neuropeptide or neuropeptide mRNA, but neuropeptides were detectable about the time that axons connect with peripheral targets. To determine the requirement for target in neuropeptide regulation, embryonic DRG neurons were isolated at times before central and peripheral connections had formed, placed in culture, and immunocytochemically assayed for CGRP and substance P. Cultured neurons expressed neuropeptides with a time course and in proportions similar to those in vivo. Thus, some neurons in the embryonic DRG seem to be intrinsically specified to later express CGRP and substance P. The percentage of CGRP-immunoreactive neurons was not changed by cell density, non-neuronal cells, neurotrophins in addition to nerve growth factor (NGF), or antibody inactivation of neurotrophin-3 in the presence of NGF. To test the role of extrinsic cues on CGRP expression, DRG neurons were co-cultured with potential target tissues. Coculture with a rat epidermal or smooth muscle cell line increased the proportion of CGRP-containing neurons, whereas primary skeletal muscle and 3T3 cells had no effects. Thus, multiple appropriate sensory neuron phenotypes arise in a regulated fashion in cultured neurons isolated before target connections have formed, and some candidate target tissues can modulate that intrinsic expression pattern. Key words: neuropeptides; substance P; calcitonin generelated peptide; neurofilament; nociceptive; sensory ganglion; target tissue; skin; neurotrophinA striking feature of the adult vertebrate sensory nervous system is the diversity of neuronal cell types that perform together to maintain homeostasis and convey information about the environment. During development, specific neurons must be generated in appropriate locations and connect discretely to both peripheral targets and the CNS for functional integrity. Thus, it is important to understand not only how the phenotype is generated but also how neurons match targets. This study examines the developmental regulation of sensory neurons containing calcitonin generelated peptide (CGRP) that predominantly contact visceral and cutaneous peripheral target end organs in vivo.Adult rat sensory neurons can express neuromodulatory neuropeptides, but the factors that regulate their initial expression remain unknown. Cutaneous afferents appear in rat proximal hindlimb on embryonic days 14 -15 (E14 -E15) and in skin of distal toes at E16 -E17 (Reynolds et al

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Section: Discussionmentioning

confidence: 58%

Section: General Culture Conditions Did Not Regulate Cgrp Expressionmentioning

confidence: 96%

Section: Cgrp Expression By Cultured Drg Neurons Was Temporally Similmentioning

confidence: 99%

Section: Cgrp Expression By Cultured Drg Neurons Was Temporally Similmentioning

confidence: 99%

Section: General Culture Conditions Did Not Regulate Cgrp Expressionmentioning

confidence: 99%

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The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

Hall

Hickman

et al. 1997

J. Neurosci.

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Time-dependence and cell-type specificity of synergistic neurotrophin actions on spiral ganglion neurons

1998

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The neurotrophins brain-derived neurotrophin (BDNF) and neurotrophin-3 (NT-3) synergistically enhance survival of spiral ganglion neurons such that simultaneous exposure to both compounds produces a larger response than would be expected from their individual effects. To elucidate the functional role of this neurotrophin interaction, we examined its temporal and cell-type specificity in vitro for both mouse and gerbil spiral ganglion neurons. Synergistic effects were transient; they were maximal within the first two postnatal days and declined during the first postnatal week. Both neurotrophins were, however, still efficacious at increasing cell survival. After postnatal day 10, the effects of coexposure to BDNF and NT-3 were additive rather than synergistic. Synergism declined more rapidly in mouse than gerbil neurons, reflecting the difference in cochlear development for each species. Only neurons without peripherin epitopes, putative type I neurons, showed synergistic survival effects; survival of peripherin-expressing neurons was purely additive. Therefore, during a restricted time period, identical neurotrophin stimuli are capable of preferentially enhancing survival of one class of neurons that compose approximately 95% of the adult spiral ganglion.

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Neurotrophin actions during the development of the peripheral nervous system

Fariñas

1999

Microsc. Res. Tech.

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Proliferation, Differentiation, and Survival of Rat Sensory Neuron Precursors in Vitro Require Specific Trophic Factors

Cited by 81 publications

References 0 publications

The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

Time-dependence and cell-type specificity of synergistic neurotrophin actions on spiral ganglion neurons

Neurotrophin actions during the development of the peripheral nervous system

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