Regulation of nerve growth factor receptor gene expression by nerve growth factor in the developing peripheral nervous system (original) (raw)
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Regulation of Nerve Growth Factor Receptor Gene Expression In Sympathetic Neurons During Development
The Journal of cell biology, 1995
We used quantitative reverse transcription (RT)/PCR to study the regulation of p75 mRNA and trkA mRNA expression in the developing sympathetic neurons of the mouse superior cervical sympathetic ganglion (SCG) in vivo and in vitro. At El3, the SCG contains proliferating cells that express many features of differentiated neurons. These immature neurons survived in culture without NGF, and NGF did not induce c-fos expression. Low levels of p75 and trkA mRNAs were expressed at this stage in vivo. There was no significant increase in the level of either trkA mRNA or p75 mRNA in El3 control cultures up to 72 h in vitro, and neither NGF nor depolarizing levels of K + ions (40 mM KCI) affected the expression of trkA mRNA. In El4 cultures, NGF induced c-fos expression in 10-15% of the neurons and enhanced the survival of a similar percentage of neurons. The proportion of neurons responding to NGF increased with age, reaching 90% in E18 cultures. The in vivo level of trkA mRNA increased markedly from E14 onward, but in contrast to sensory neurons (in which p75 and trkA mRNA levels increase in parallel), the level of trkA mRNA initially
Developmental and regional expression of β-nerve growth factor receptor mRNA in the chick and rat
Neuron, 1988
The presence of nerve growth factor (NGF) mRNA and protein in the rat central nervous system is documented. Blot-hybridization analysis showed an abundance of NGF mRNA in the hippocampus, cerebral cortex, and olfactory bulb. Enzyme immunoassay confirmed significant levels of a NGF-like protein in the hippocampus and cerebral cortex. Bioassay of a NGF-like immunoaffinity-purified protein from these regions was physiologically indistinguishable from NGF. Immunohistochemistry revealed a widespread distribution of NGF-like reactivity in the adult brain, preferentially in fiber tracts. NGF mRNA accumulation began at birth, with adult levels reached 3 weeks postnatally. Enzyme immunoassay detected the presence of a NGF-like protein in the embryonic rat brain. Postnatally, the level of NGF-like protein reached a maximum at 3 weeks. Additionally, a distinct fetal form of NGF may exist.
Annals of the New York Academy of Sciences, 1991
In newborn rats the levels of nerve growth fa tor (NGF) mRNA (mRNANGF) and NGF receptor mRNA ( A') in the sciatic nerve were 10 and 120 times higher, r pectively, than in adult animals. mRNAL levels decreased st adily from birth, approaching adult levels by the third stnatal week, whereas mRNANUF levels decreased only after th first postnatal week, although also reaching adult levels by the third week. Transection of the adult sciatic nerve resulted in a marked biphasic increase in mRNANGF with time. On the p oximal side of the cut, this increase was confined to the area immediately adjacent to the cut; peripherally, a similar biphasic increase was present in all segments. mRNAL levels were al markedly elevated distal to the transection site, in agreem nt with previous results obtained by immunological methods aniuchi, M., Clark, H. B. & Johnson, E. M., Jr. (1986) P oc. Nal. Acad. Sci. USA 83, 4094-4098]. Following a crush le ion (allowing regeneration), the mRNA1 levels were rapidly
The EMBO Journal, 1984
We have developed a sensitive assay for the quantification of nerve growth factor mRNA (mRNANGF) in various tissues of the mouse using in vitro transcribed RNANGF. Probes of both polarities were used to determine the specificity of the hybridization signals obtained. Comparison of NGF levels with its mRNA revealed that both were correlated with the density of sympathetic innervation. Thus, vas deferens contained high levels of both NGF and mRNANGF, whereas skeletal muscle levels were barely detectable, indicating that in peripheral tissues NGF levels are primarily regulated by the quantity of mRNANGF and not by the rate of processing of NGF precursor to NGF. However, although superior cervical ganglia contained the highest levels of NGF, its mRNA was barely detectable. Thus, the high levels of NGF in sympathetic ganglia result from retrograde axonal transport rather than local synthesis. The quantity of NGF found in the submandibular glands of female animals was three orders of magnitude higher than expected from their mRNA levels. This observation is discussed in the context of the difference between the mechanism of storage and exocytosis of exocrine glands versus the constitutive release from other tissues.
Neuroscience Letters, 2008
Nerve growth factor (NGF) and neurotrophin-3 (NT3) play distinctive roles in sympathetic axon growth and target field innervation and are required for sympathetic neuron survival in vivo. To ascertain if these neurotrophins selectively regulate the expression of genes that determine the functional characteristics of differentiated sympathetic neurons, we measured the mRNA levels for several such genes in the superior cervical ganglion of NGF −/− , NT3 −/− and wild type mouse embryos at a stage before excessive neuronal loss occurs in the absence of these neurotrophins. Despite the extensively documented ability of NGF to regulate the noradrenergic phenotype of sympathetic neurons, we found that tyrosine hydroxylase (TH) and dopamine  hydroxylase (DH) mRNA levels were normal in NGF −/− embryos, but significantly reduced in NT3 −/− embryos. In contrast, the 2 nicotinic acetylcholine receptor and PACAP receptor 1 mRNA levels were normal in NT3 −/− embryos, but significantly reduced in NGF −/− embryos. Studies of mice lacking neurotrophin receptors suggested that the effects of NGF on gene expression require TrkA whereas those of NT3 require TrkA and p75 NTR. These findings demonstrate that endogenous NGF and NT3 have distinctive and separate effects on gene expression in early sympathetic neurons and that these selective effects on gene expression require a different combination of neurotrophin receptors.
‘Mature’ nerve growth factor is a minor species in most peripheral tissues
Neuroscience Letters, 2005
The classic neurotrophin hypothesis is based on the idea that innervating neurons derive 'mature' neurotrophin provided by the target for their survival. Yet large precursor forms of the neurotrophin nerve growth factor (NGF) have been reported in both central and peripheral tissues. In the present study, immunoblotting was used to survey peripheral tissues containing NGF-responsive neurons and to characterize various NGF species. These results demonstrate that 'mature' forms of NGF, i.e., the 13 and 16 kDa species, are rare in sympathetic and sensory ganglia and in their peripheral targets, and that large molecular weight NGF precursors are abundant. In addition, certain NGF forms predominate in a given tissue, with each tissue exhibiting a characteristic NGF expression pattern. These findings suggest that NGF processing in peripheral tissues and in NGF-responsive ganglia may involve a variety of NGF species.
Journal of Biological Chemistry, 2009
Nerve growth factor (NGF) is produced as a precursor called pro-nerve growth factor (proNGF), which is secreted by many tissues and is the predominant form of NGF in the central nervous system. In Alzheimer disease brain, cholinergic neurons degenerate and can no longer transport NGF as efficiently, leading to an increase in untransported NGF in the target tissue. The protein that accumulates in the target tissue is proNGF, not the mature form. The role of this precursor is controversial, and both neurotrophic and apoptotic activities have been reported for recombinant proNGFs. Differences in the protein structures, protein expression systems, methods used for protein purification, and methods used for bioassay may affect the activity of these proteins. Here, we show that proNGF is neurotrophic regardless of mutations or tags, and no matter how it is purified or in which system it is expressed. However, although proNGF is neurotrophic under our assay conditions for primary sympathetic neurons and for pheochromocytoma (PC12) cells, it is apoptotic for unprimed PC12 cells when they are deprived of serum. The ratio of tropomyosin-related kinase A to p75 neurotrophin receptor is low in unprimed PC12 cells compared with primed PC12 cells and sympathetic neurons, altering the balance of proNGFinduced signaling to favor apoptosis. We conclude that the relative level of proNGF receptors determines whether this precursor exhibits neurotrophic or apoptotic activity.
Distribution of neuronal receptors for nerve growth factor in the rat
The Journal of Neuroscience, 1986
To survey the distribution of neuronal receptors for NGF, sections of the rat brain, spinal cord, and peripheral ganglia were incubated in vitro with radioiodinated NGF and examined by autoradiography. NGF binds selectively with high affinity to most sympathetic neurons and many primary sensory neurons together with their intraspinal or intramedullary axons. In autoradiographs of the brain, labeled neuronal perikarya are seen in the basal forebrain, the caudate-putamen, the medulla oblongata, the ventral cochlear nucleus, and the dorsal nucleus of the lateral lemniscus. The distribution of neurons binding NGF resembles the distribution of cholinergic neurons in the forebrain, but these 2 systems overlap very little in the brain stem. In extracts of the brain or spinal cord enriched for plasma membranes, avid binding sites are regionally manifest with properties similar to those of fetal peripheral neurons. The localization of neurons expressing the high- affinity receptor for NGF de...