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Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2004 Mar 03; Vol. 24 (9), pp. 2236-46. - Publication Year :
- 2004
-
Abstract
- 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
- Subjects :
- Animals
Antigens, CD biosynthesis
Apoptosis genetics
Gene Expression Regulation physiology
Mesoderm metabolism
Motor Neurons cytology
RNA, Messenger metabolism
Rats
Rats, Sprague-Dawley
Receptors, Tumor Necrosis Factor biosynthesis
Receptors, Tumor Necrosis Factor, Type I
Somites cytology
Somites physiology
Tumor Necrosis Factor-alpha genetics
Apoptosis physiology
Gene Expression Regulation, Developmental physiology
Macrophages metabolism
Motor Neurons metabolism
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 24
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 14999074
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.4464-03.2004