Neurotrophic activity in embryonic chick brain: early appearance and differential regional distribution

Homogenate extracts were prepared from various regions of the embryonic chick brain from E6 to E19. The extracts were applied to cultured dorsal root ganglia (DRGs), sympathetic ganglion cells, PC12 cells and E5 spinal cord neurons. Potent neurotrophic activity with respect to DRGs was found in an extract from the forebrain (FBX) from the earliest stage assayed (E6). This activity was comparable to that of nerve growth factor (NGF), and it was not appreciably altered during later stages. By E8, extracts prepared from the optic lobe also induced responsiveness, although to a lesser extent than the FBX and NGF. At E12-19, extracts from the hippocampus (HCX) and cerebellum (CBX) were also tested. Activity found in the HCX resembled that in the FBX, but responsiveness to the CBX was similar to that in control (unsupplemented) cultures. The responsiveness of sympathetic neurons in the FBX was comparable to that with NGF. The FBX induced only moderate differentiation of PC12 cells, and spinal cord neurons were not responsive. Antibodies to NGF and basic fibroblast growth factor did not diminish the influence of the FBX, and the FBX and NGF when combined had synergistic effects. The results demonstrate potent neurotrophin-like activity in the embryonic brain at much earlier stages than had previously been seen, with differential regional and temporal distributions.