Subpopulations of rat B2(+) neuroblasts exhibit differential neurotrophin responsiveness during sympathetic development

Sympathetic neurons comprise a population of postmitotic, tyrosine hydroxyl ase expressing cells whose survival is dependent upon nerve growth factor ( NGF) both in vivo and in vitro. However, during development precursors to r at sympathetic neurons in the thoracolumbar region are not responsive to NG F because they lack the signal transducing NGF receptor, trkA. We have prev iously shown that acquisition of trkA expression is sufficient to confer a functional response to NGF. Here we describe four subpopulations of thoraco lumbar sympathetic neuroblasts which are mitotically active and unresponsiv e to NGF at E13.5 of rat gestation, but differ based upon their neurotrophi c responsiveness in vitro. The survival in culture of the largest sympathet ic subpopulation is mediated by neurotrophin-3 (NT-3) or glial-derived neur otrophic factor (GDNF), whereas the cell survival of two smaller subpopulat ions of neuroblasts are mediated by either solely GDNF or solely NT-3. Fina lly, we identify a subpopulation of sympathetic neuroblasts in the thoracol umbar region whose survival, exit from the cell cycle, induction of trkA ex pression, and consequent acquisition of NGF responsiveness in culture appea r to be neurotrophin independent and cell autonomous. These subpopulations reflect the diversity of neurotrophic actions that occur in the proper deve lopment of sympathetic neurons. (C) 2000 Academic Press.