Characterization of a cardiac muscle factor required for the survival of cultured parasympathetic neurones

Bonyhady, Rae E.; Hendry, Ian A.; Hill, Caryl E.; McLennan, Ian S.

doi:10.1016/0304-3940(80)90326-2

Cited by 59 publications

(15 citation statements)

References 14 publications

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“…Activity in the choroid does not seem to play the same role in cell death as does activity in the ciliary body and iris . The inability to derive support from the cultured choroid is even more puzzling given that other, nontarget, tissues, such as bovine heart (Bonyhady et al, 1980) and rat hippocampus (Heacock et al, 1986), produce CNTFs. This does not preclude the possibility that the cultured choroid is modified sufficiently to prevent it from performing its trophic role.…”

Section: Discussionmentioning

confidence: 99%

Cultured smooth muscle targets lack survival activity for ciliary ganglion neurons

Creedon

1988

J. Neurosci.

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Cultured neurons require specific trophic agents in order to survive. This dependence is thought to resemble the neuron-target interdependence that develops in vivo during synaptogenesis and neuronal cell death. The notion that neurons in general derive trophic support from their synaptic targets is based primarily on studies of peripheral neurons and motor neurons. To assess the general applicability of this nerve-target relationship, we tested the ability of vascular smooth muscle (VSM) to support dissociated neurons from the chick ciliary ganglion. The ciliary ganglion contains 2 distinct neuronal populations, one of which innervates striated muscle, the other VSM. Striated muscle cocultures are known to support all of the neurons in the ganglion for extended periods. Dissociated neurons were therefore cocultured in microwells containing VSM derived from the rat or chick aorta and from the choroid coat of the chick eye. Surviving neurons were counted after 1, 2, 5, and 7 d. Striated muscle is able to support full neuronal survival in the same assay. However, in no case was VSM capable of contributing to neuronal survival in vitro. The neurons in the VSM cocultures were able to form neurites and make contacts with their putative targets, as confirmed by scanning electron and light microscopy. The presence of viable and differentiated smooth muscle cells was demonstrated in the cultures by transmission electron microscopy and analysis of smooth muscle alpha-actin. The failure of VSM and even the choroid target tissue to support the survival of their innervating neurons suggests that novel mechanisms may operate to provide trophic support for neurons innervating VSM targets.

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Section: Discussionmentioning

confidence: 99%

Cultured smooth muscle targets lack survival activity for ciliary ganglion neurons

Creedon

1988

J. Neurosci.

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“…Moreover, CNTF-like activities, among them discrete entities with an apparent molecular weight close to the chicken and mammalian CNTF (19,20), have innervation. With the chicken eye (7) and mammalian (9) CNTF, two distinct molecules sharing the ability to support the in vitro survival of a unique spectrum of embryonic neurons (cf.…”

Section: Discussionmentioning

confidence: 99%

Neuroblastoma cells contain a trophic factor sharing biological and molecular properties with ciliary neurotrophic factor.

Heymanns

Unsicker

1987

Proc. Natl. Acad. Sci. U.S.A.

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Ciliary neurotrophic factor (CNTF) is a protein supporting the in vitro survival of a characteristic spectrum of embryonic chicken and rat peripheral neurons. High-speed supernatants of extracts from two neuroblastoma (NB) cell lines-the mouse C 1300 N2a and the human IMR 32-mimic the effects of CNTF on identical target neurons. Promotion of survival is dose-dependent with an ED50 of 80 ,ug (IMR 32) and 140 ,Ag (C 1300 N2a) of protein per ml and saturable at plateau values for surviving neurons identical to those achieved with purified CNTF. Small amounts of a CNTF-like material are also detectable in medium conditioned by NB cells. The activity is destroyed by heat and trypsin and not blocked by antibodies to (mouse) nerve growth factor. Unlike the neurite-promoting and neuronal-survival modulating agent laminin, it cannot be depleted on poly(L-a-ornithine)-coated plastic surfaces. NB IMR 32 cell extracts were electrophoresed using NaDodSO4/ PAGE and transferred to nitrocellulose. Ciliary ganglion neurons seeded on the blotting paper in culture medium lacking CNTF ("cell blot") exclusively survive on two distinct bands with apparent molecular masses of 24 and 48 kDa. Twenty-four kilodaltons is the molecular mass of a CNTF purified from rat sciatic nerve. These results suggest that NB cells may contain a CNTF-like protein and provide further evidence that neurons may store neurotrophic factors. Purified (chicken) CNTF failed to affect proliferation and neurite growth of NB cells. The biological relevance of CNTF for NB cells, therefore, remains to be elucidated.Naturally occurring cell death is a process during the development of the nervous system that is important for morphogenesis and the establishment of proper neuronal connections (1). In several neuronal systems investigated, neuronal cell death is determined to varying extents by neurotrophic factors (NTFs) that are made available to neurons by their respective target tissues. A well-documented example of a NTF is nerve growth factor (NGF) whose structure, synthesis, and functions have been most extensively studied (2). Extrapolating from NGF (and target organ)-regulated neuron death, it seems reasonable to suggest that neurons as target cells to other neurons may supply these with NTFs (1, 3). However, evidence for NTFs of neuronal origin is still scarce (3), a major reason possibly being that their demonstration requires purified, large and homogeneous populations of neurons.We have found that adrenal medullary chromaffin cellsi.e., modified sympathetic neurons-store and secrete trophic activities that support the in vitro survival of a large number of neurons dissociated from embryonic and neonatal peripheral and central nervous tissues (4-6). The molecular characteristics of these agents have only partially been revealed, but they do not seem to resemble NGF. Neuroblastoma (NB) cells are closely related to sympathetic neurons and chromaffin cells. We report here that two NB cell lines, the human IMR 32 and mouse C 1300 N2a, contain a NTF activ...

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“…A number of survival-promoting factors for ciliary ganglion neurons were reported in a variety of sources: heart and muscle conditioned medium (Helfand et al, 1976;Berg, 1977, 1979) and extracts of chicken embryos and bovine heart (Bonyhady et al, 1980). Many of these survival-promoting activities had the same apparent molecular weight and stability to denaturation by SDS (Collins, 1985 ) .…”

Section: Molecules That Support Neuronal Survivalmentioning

confidence: 96%

Target‐derived molecules that influence the development of neurons in the avian ciliary ganglion

Nishi

1994

J. Neurobiol.

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The developing avian ciliary ganglion has been a particularly amenable system for the identification, isolation, and characterization of putative target-derived molecules that mediate retrograde interactions. To date a number of biochemically distinct activities that regulate neuronal survival, transmitter phenotype, and chemosensitivity of ciliary ganglion neurons have been identified. Of these, only two survival-promoting molecules have been purified to homogeneity: ciliary neurotrophic factor and a related molecule, growth-promoting activity. A somatostatin-inducing activity found in cultured choroid cells is very likely to be chick activin A. Other molecules that regulate acetylcholine and acetylcholine receptor expression comigrate on a gel filtration column at a molecular weight of 50-60 kD, but they have yet to be isolated. Once molecules that mimic retrograde influences are identified, a number of criteria must be met before their physiological significance can be established. These criteria are (1) availability of the molecule from the target at the appropriate time in development; (2) ability of the neurons to respond to the molecule at the appropriate time in development; (3) demonstration that blocking the activity or availability of the molecule is able to block the target-derived developmental change expressed in the neurons. Of the molecules that are thought to retrogradely influence ciliary neuron development, only growth-promoting activity is known to meet criteria 1 and 2, and experiments are currently underway to test whether inhibition of growth-promoting activity in vivo will exacerbate normal cell death.

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Characterization of a cardiac muscle factor required for the survival of cultured parasympathetic neurones

Cited by 59 publications

References 14 publications

Cultured smooth muscle targets lack survival activity for ciliary ganglion neurons

Cultured smooth muscle targets lack survival activity for ciliary ganglion neurons

Neuroblastoma cells contain a trophic factor sharing biological and molecular properties with ciliary neurotrophic factor.

Target‐derived molecules that influence the development of neurons in the avian ciliary ganglion

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