Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death.
J Neurosci
; 24(9): 2236-46, 2004 Mar 03.
Article
en En
| MEDLINE
| ID: mdl-14999074
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
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Necrosis Tumoral alfa
/
Apoptosis
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Regulación del Desarrollo de la Expresión Génica
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Macrófagos
/
Neuronas Motoras
Límite:
Animals
Idioma:
En
Revista:
J Neurosci
Año:
2004
Tipo del documento:
Article
País de afiliación:
Francia