Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons

Crowley, Craig; Spencer, Susan D.; Nishimura, Merry; Chen, Karen S.; Pitts-Meek, Sharon; Armaninl, Mark P.; Ling, Lanway H.; McMahon, Stephen B.; Shelton, David L.; Levinson, Arthur D.; Phillips, Heidi S.

doi:10.1016/0092-8674(94)90378-6

Cited by 992 publications

(699 citation statements)

References 33 publications

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“…The idea of TrkC being a DR is particularly attractive while analyzing data from knockout mice for neurotrophins and their respective receptors. Indeed, inactivation of TrkA or NGF in mice results in the same amount of sensory neuron loss at birth (that is, nociceptive neurons) (Crowley et al, 1994). Similarly, inactivation of either TrkB or brain-derived neurotrophic factor results in an equivalent loss of mechanoceptive neurons (Ernfors et al, 1994;Minichiello et al, 1995).…”

Section: Role Of Drs During Embryonic Developmentmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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Section: Role Of Drs During Embryonic Developmentmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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“…In the periphery, NGF and NT-3 are produced by target tissues, internalized by the innervating sympathetic and/or sensory neuron, and retrogradely transported to the cell body (Thoenen and Barde 1980;Schwab et al 1982;Zhou and Rush 1996;Zhou et al 1997;Kuruvilla et al 2004), where they carry out their survival activities. NGF is essential for the survival of sympathetic neurons during development (Gorin and Johnson 1980;Crowley et al 1994) as well as in adulthood (Ruit et al 1990;Ghasemlou et al 2004). NT-3 also is important for the survival of sympathetic neurons (Zhou and Rush 1995;Rush et al 1997;Francis et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Regulation of NGF and NT-3 protein expression in peripheral targets by sympathetic input

2007

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Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are target-derived proteins that regulate innervating sympathetic neurons. Here, we used western blot analysis to investigate changes in NGF and NT-3 protein in several peripheral tissues following loss of sympathetic input. Following removal of the superior cervical ganglion (SCG), large molecular weight (MW) NGF species, including proNGF-A, were increased in distal intracranial SCG targets, such as pineal gland and extracerebral blood vessels (bv). Mature NGF was a minor species in these tissues and unchanged following sympathectomy. Large MW NGF species also were increased when sympathectomy was followed by in vivo NGF administration. Mature NT-3, which was abundant in controls, was significantly decreased in these targets following sympathetic denervation. The decrease in mature NT-3 was enhanced following NGF administration. The trigeminal ganglion, which provides sensory input to these targets, showed increased NGF, but decreased NT-3, in these treatments, demonstrating that decreased NT-3 at the targets did not result from enhanced NT-3 uptake. Unlike pineal gland and extracerebral bv, the external carotid artery, an extracranial proximal SCG target, showed no change in NGF following denervation, and mature NT-3 was significantly increased. Following NGF administration, NT-3 was significantly decreased. We provide evidence for sympathetic regulation of NGF and NT-3 in peripheral targets and that elevated NGF can depress NT-3. The differential response in distal and proximal adult targets is consistent with the idea that neurons innervating proximal and distal targets may serve different roles in regulating neurotrophin protein. In addition, we conclude that previous ELISA results showing increased NGF protein following sympathetic denervation may have resulted from increases in large MW species, rather than an increase in mature NGF.

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“…Differentiation of normal dorsal root ganglion cells with NGF results in mature nerve cells dependent on trophic factors (Crowley et al, 1994;Smeyne et al, 1994) and we wondered whether differentiated HTLA230 would demonstrate a similar phenotype. Hence, HTLA230 cells were differentiated with GDNF, CNTF and NGF and the medium was replaced with medium from which growth factors were omitted.…”

Section: Neuroblastoma Differentiation S Peterson and E Bogenmannmentioning

confidence: 99%

The RET and TRKA pathways collaborate to regulate neuroblastoma differentiation

Peterson

Bogenmann

2004

Oncogene

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Neuroblastoma (NB) is a childhood cancer that arises in the adrenal gland and often shows differentiated neuronal and glial elements. The RET receptor signal pathway is functional in most NB, while loss of nerve growth factor (NGF) receptor (trkA) gene expression correlates with an aggressive phenotype. Thus, we hypothesized that the RET and TRKA signal pathways collaborate to instruct NB differentiation, reminiscent of normal neuronal maturation. Here, we demonstrate that activation of the RET receptor by glial cell line-derived neurotrophic factor (GDNF) increases expression of the RET receptor complex in a panel of malignant human NB cell lines, indicative of a positive feedback mechanism. GDNF also induces growth cessation concomitant with an arrest of cells in the G 0 /G 1 phase of the cell cycle. Furthermore, GDNF synergizes with ciliary neurotrophic factor (CNTF) to enhance TRKA receptor expression, thereby strengthening the NGF-mediated differentiation signal. Differentiated NB cells downregulate expression of the amplified N-myc gene, concurrent with the arrest of cell proliferation, while expressing neuron-specific markers (i.e., SCG10). Interestingly, maintenance of differentiated NB cells in culture is independent of the trophic activity of GDNF, but depends on TRKA signaling, thereby reenacting the differentiation of normal sympathoadrenal (SA) progenitor cells.

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Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons

Cited by 992 publications

References 33 publications

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Regulation of NGF and NT-3 protein expression in peripheral targets by sympathetic input

The RET and TRKA pathways collaborate to regulate neuroblastoma differentiation

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