Macrophage-Derived Tumor Necrosis Factor α, an Early Developmental Signal for Motoneuron Death

• DOI: 10.1523/jneurosci.4464-03.2004
• Publication Date: 2004-03-03T18:02:46Z
• Authors: Frédéric Sedel; Catherine Béchade; Sheela Vyas; Antoine Triller
• Keywords: Motor Neurons; Tumor Necrosis Factor-alpha; Macrophages; Gene Expression Regulation, Developmental; Apoptosis; Receptors, Tumor Necrosis Factor; Rats; Mesoderm; Rats, Sprague-Dawley; 03 medical and health sciences; 0302 clinical medicine; Gene Expression Regulation; Somites; Antigens, CD; Receptors, Tumor Necrosis Factor, Type I; Animals; RNA, Messenger

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 rats is 72-48 hr before programmed cell death. Half the motoneurons isolated from peripheral tissues E12 escape death, whereas 90% of enter program. The surrounding somite commits to This effect requires macrophage cells, mimicked by tumor necrosis factor α (TNFα), inhibited anti-TNFα antibodies. In vivo , TNFα detected within macrophages, TNF receptor 1 (TNFR1) precisely E13. Although motoneuron normally -/- mice, this process significantly reduced TNFR1 mice. Thus, acquire competence die, onset extrinsic signals such as macrophage-derived