BMP Enhances Transcriptional Responses to NGF During PC12 Cell Differentiation

Lönn, Peter; Zaia, Kimberly; Israelsson, Charlotte; Althini, Susanna; Usoskin, Dmitry; Kylberg, Annika; Ebendal, Ted

doi:10.1007/s11064-005-6868-6

Cited by 15 publications

(14 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Induction of Egr2-4 transcripts by NGF in PC12 cells has also been shown, however, these studies did not evaluate protein levels [10, 62, 63]. To our knowledge, effects of NGF on WT1 expression in PC12 cells has not been previously described.…”

Section: Resultsmentioning

confidence: 99%

Role for Egr1 in the Transcriptional Program Associated with Neuronal Differentiation of PC12 Cells

et al. 2017

View full text Add to dashboard Cite

PC12 cells are a well-established model to study how differences in signal transduction duration can elicit distinct cell behaviors. Epidermal growth factor (EGF) activates transient ERK signaling in PC12 cells that lasts 30–60 min, which in turn promotes proliferation; nerve growth factor (NGF) activates more sustained ERK signaling that lasts 4–6 h, which in turns induces neuronal differentiation. Data presented here extend a previous study by Mullenbrock et al. (2011) that demonstrated that sustained ERK signaling in response to NGF induces preferential expression of a 69-member gene set compared to transient ERK signaling in response to EGF and that the transcription factors AP-1 and CREB play a major role in the preferential expression of several genes within the set. Here, we examined whether the Egr family of transcription factors also contributes to the preferential expression of the gene set in response to NGF. Our data demonstrate that NGF causes transient induction of all Egr family member transcripts, but a corresponding induction of protein was detected for only Egr1 and 2. Chromatin immunoprecipitation experiments provided clearest evidence that, after induction, Egr1 binds 12 of the 69 genes that are preferentially expressed during sustained ERK signaling. In addition, Egr1 expression and binding upstream of its target genes were both sustained in response to NGF versus EGF within the same timeframe that its targets are preferentially expressed. These data thus provide evidence that Egr1 contributes to the transcriptional program activated by sustained ERK signaling in response to NGF, specifically by contributing to the preferential expression of its target genes identified here.

show abstract

Section: Resultsmentioning

confidence: 99%

Role for Egr1 in the Transcriptional Program Associated with Neuronal Differentiation of PC12 Cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Some candidates are the BMPs and neurosteroids. Studies by Lopez-Coviella and colleagues have shown that BMP-9 is a robust factor for induction and maintenance of the cholinergic phenotype in vitro [60,61], which also synergizes with NGF to enhance neuronal transcriptional response [30,62]. In addition, neurosteroids such as estrogen and retinoic acid have also been shown to up-regulate the cholinergic phenotype in the septal basal forebrain [63,64].…”

Section: Discussionmentioning

confidence: 99%

Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons

Lazo

Mauna

Pissani

et al. 2010

Mol Neurodegeneration

View full text Add to dashboard Cite

BackgroundSeptal cholinergic neurons account for most of the cholinergic innervations of the hippocampus, playing a key role in the regulation of hippocampal synaptic activity. Disruption of the septo-hippocampal pathway by an experimental transection of the fimbria-fornix drastically reduces the target-derived trophic support received by cholinergic septal neurons, mainly nerve growth factor (NGF) from the hippocampus. Axotomy of cholinergic neurons induces a reduction in the number of neurons positive for cholinergic markers in the medial septum. In several studies, the reduction of cholinergic markers has been interpreted as analogous to the neurodegeneration of cholinergic cells, ruling out the possibility that neurons lose their cholinergic phenotype without dying. Understanding the mechanism of cholinergic neurodegeneration after axotomy is relevant, since this paradigm has been extensively explored as an animal model of the cholinergic impairment observed in neuropathologies such as Alzheimer's disease.The principal aim of this study was to evaluate, using modern quantitative confocal microscopy, neurodegenerative changes in septal cholinergic neurons after axotomy and to assess their response to delayed infusion of NGF in rats.ResultsWe found that there is a slow reduction of cholinergic cells labeled by ChAT and p75 after axotomy. However, this phenomenon is not accompanied by neurodegenerative changes or by a decrease in total neuronal number in the medial septum. Although the remaining axotomized-neurons appear healthy, they are unable to respond to delayed NGF infusion.ConclusionsOur results demonstrate that at 3 weeks, axotomized cholinergic neurons lose their cholinergic phenotype without dying and down-regulate their NGF-receptors, precluding the possibility of a response to NGF. Therefore, the physiological role of NGF in the adult septal cholinergic system is to support phenotypic differentiation and not survival of neurons. This evidence raises questions about the relationship between transcriptional regulation of the cholinergic phenotype by retrograde-derived trophic signaling and the transcriptional changes experienced when retrograde transport is impaired due to neuropathological conditions.

show abstract

“…In addition, although the literature contains many in vitro studies showing the neurotrophic function of BMPs [1,3,10,12,15], their distribution and the pattern of expression has not previously been demonstrated in vivo. We therefore determined (1) whether BMP-2, -7 and their receptors (BMPRs) are expressed in the normal sciatic nerves of rats; (2) if so, where they are distributed in the injured nerve; and (3) whether BMPs and BMPRs are expressed in the vessels within the perineurium after the nerve transection.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies suggest treatment with a combination of BMPs and other neurotrophic factors can substantially increase neurite outgrowth [1,3,15] and that the application of BMPs to Schwann cells increased the level of neurotrophic factors expressed [12]. Based on these results, Kinameri et al speculated that the autocrine action of BMP-2 regulated expression of important neurotrophic factors in Schwann cells [12].…”

Section: Discussionmentioning

confidence: 99%

Are BMPs Involved in Normal Nerve and Following Transection?: A Pilot Study

Tsujii

Akeda

Iino

et al. 2009

Clin Orthop Relat Res

View full text Add to dashboard Cite

Bone morphogenic proteins (BMPs) may have neurotrophic functions but there is limited evidence of these functions in the peripheral nervous system. We therefore investigated the expression of BMPs and BMP receptors (BMPRs) in normal and injured peripheral nerves. In 10 of 15 Sprague-Dawley rats, a 3-mm segment of sciatic nerve was resected at the trifurcation in the thigh. One day (n = 5) and 7 days (n = 5) after transection, proximal and distal stumps were removed and immunohistochemically analyzed for BMP-2, -7, BMPR-1A, -1B, and -2. The other five animals served as normal controls. In normal nerves, BMP-2 expression was localized at Ranvier's node, and BMP-7 and BMPR-1B were expressed in several axon-Schwann cell units, whereas other receptors were not expressed. After nerve transection, BMP-7 expression was upregulated at both proximal and distal stumps along with Schwann cell columns during Wallerian degeneration. BMPRs were also upregulated compared with the normal nerve. The upregulation in BMP expression after nerve transection suggests that BMPs may play a role in the healing response of the peripheral nerve.

show abstract

BMP Enhances Transcriptional Responses to NGF During PC12 Cell Differentiation

Cited by 15 publications

References 39 publications

Role for Egr1 in the Transcriptional Program Associated with Neuronal Differentiation of PC12 Cells

Role for Egr1 in the Transcriptional Program Associated with Neuronal Differentiation of PC12 Cells

Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons

Are BMPs Involved in Normal Nerve and Following Transection?: A Pilot Study

Contact Info

Product

Resources

About