Motoneuron-derived neurotrophin-3 is a survival factor for PAX2-expressing spinal interneurons.
Rat spinal cord interneurons undergo programmed cell death shortly after birth. We investigated here whether cell death of interneurons could be regulated by trophic factors produced by motoneurons, one of their main targets. To test this hypothesis, we studied the effect of the selective destruction of motoneurons on the survival of interneurons in organotypic cultures of embryonic rat spinal cords. Motoneurons were eliminated by an anti-p75(NTR)-specific immunotoxin (192 IgG-saporin). We then observed a decrease of 28% in the number of ventral spinal interneurons immunoreactive (IR) for the homeoprotein PAX2. This was correlated with an increase in the number of apoptotic nuclei in the same area. Because neurotrophin-3 (NT-3) is specifically produced by motoneurons and because interneurons express the NT-3 high-affinity receptor trkC, we examined the role of NT-3 in the survival of PAX2-IR interneurons. Addition of NT-3 to 192 IgG-saporin-treated explants rescued ventral PAX2-IR interneurons. Depletion of secreted NT-3 by anti-NT-3 antibodies induced 66% loss of ventral PAX2-IR interneurons. We conclude that motoneuron-derived NT-3 is a trophic factor for ventral PAX2-IR interneurons.
Béchade
Catherine
C
Laboratoire de Biologie Cellulaire de la Synapse Normale et Pathologique, Institut National de la Santé et de la Recherche Médicale U497, Ecole Normale Supérieure, 75005 Paris, France. bechade@wotan.ens.fr
Mallecourt
Catherine
C
Sedel
Frédéric
F
Vyas
Sheela
S
Triller
Antoine
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D000922:Immunotoxins / Q000494:pharmacology; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases; D020933:Neurotrophin 3 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D051762:PAX2 Transcription Factor; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*
C085696:192 IgG-saporin; D000906:Antibodies; D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D000922:Immunotoxins; D020933:Neurotrophin 3; D051762:PAX2 Transcription Factor; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D014157:Transcription Factors; D009699:N-Glycosyl Hydrolases; D000076985:Saporins