A reciprocal cell-cell interaction mediated by NT-3 and neuregulins controls the early survival and development of sympathetic neuroblasts.
Neurotrophin 3 (NT-3) can support the survival of some embryonic sympathetic neuroblasts before they become nerve growth factor dependent. We show that NT-3 is produced in vivo by nonneuronal cells neighboring embryonic sympathetic ganglia. NT-3 mRNA is produced by these nonneuronal cells in vitro and is up-regulated by platelet-derived growth factor, ciliary neurotrophic factor, and glial growth factor 2 (a neuregulin). Nonneuronal cell-conditioned medium promotes survival and induces TrkA expression in isolated sympathetic neuroblasts, and this activity is blocked by anti-NT-3 antibody. Neuroblasts also enhance NT-3 production by nonneural cells. Neuroblasts synthesize several forms of neuregulin, and antibodies to neuregulin attenuate the effect of the neuroblasts on the nonneuronal cells. These data suggest a reciprocal cell-cell interaction, in which neuroblast-derived neuregulins promote NT-3 production by neighboring nonneuronal cells, which in turn promotes neuroblast survival and further differentiation.
Verdi
J M
JM
Division of Biology 216-76, California Institute of Technology, Pasadena 91125, USA.
Groves
A K
AK
Fariñas
I
I
Jones
K
K
Marchionni
M A
MA
Reichardt
L F
LF
Anderson
D J
DJ
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013997:Time Factors
D009414:Nerve Growth Factors; D012333:RNA, Messenger