RGD Reference Report - Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death. - Rat Genome Database

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Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death.

Authors: Sedel, F  Bechade, C  Vyas, S  Triller, A 
Citation: Sedel F, etal., J Neurosci. 2004 Mar 3;24(9):2236-46.
RGD ID: 1580294
Pubmed: PMID:14999074   (View Abstract at PubMed)
PMCID: PMC6730439   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.4464-03.2004   (Journal Full-text)

Mechanisms inducing neuronal death at defined times during embryogenesis remain enigmatic. We show in explants that a developmental switch occurs between embryonic day 12 (E12) and E13 in rats that is 72-48 hr before programmed cell death. Half the motoneurons isolated from peripheral tissues at E12 escape programmed cell death, whereas 90% of motoneurons isolated at E13 enter a death program. The surrounding somite commits E12 motoneurons to death. This effect requires macrophage cells, is mimicked by tumor necrosis factor alpha (TNFalpha), and is inhibited by anti-TNFalpha antibodies. In vivo, TNFalpha is detected within somite macrophages, and TNF receptor 1 (TNFR1) is detected within motoneurons precisely between E12 and E13. Although motoneuron cell death occurs normally in TNFalpha-/- mice, this process is significantly reduced in explants from TNFalpha-/- and TNFR1-/- mice. Thus, embryonic motoneurons acquire the competence to die, before the onset of programmed cell death, from extrinsic signals such as macrophage-derived TNFalpha

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of neuron apoptotic process  IMP 1580294 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)


Additional Information