ROLE OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN REGULATING THE EXPRESSION OF NERVE GROWTH-FACTOR AND NEUROTROPHIN-3 MESSENGER-RNA LEVELS IN EMBRYONIC CUTANEOUS CELLS AT DIFFERENT STAGES OF DEVELOPMENT

We have investigated if transforming growth factor-beta (TGF-beta) iso forms influence the level of expression of nerve growth factor (NGF) m RNA and neurotrophin-3 (NT-3) mRNA in embryonic tissues innervated by neurons that depend on NGF and NT-3 for survival. Presumptive dermal a nd epidermal cells from the maxillary territory of the embryonic mouse trigeminal ganglion were cultured in defined medium during the early stages of innervation when trigeminal neurons switch their survival de pendence from NT-3 to NGF. In E11 and E12 cultures, when the in vivo l evels of NGF mRNA and NT-3 mRNA are increasing, TGF-beta 1, TGF-beta 2 and TGF-beta 3 each increased the level of NGF mRNA but had no effect on NT-3 mRNA. In E13 cultures, when the in vivo levels of NGF mRNA an d NT-3 mRNA reach a peak (relative to actin mRNA) prior to a marked fa ll in the level of NT-3 mRNA and a gradual decrease in the level of NG F mRNA, TGF-beta s promoted further increases in the level of NGF mRNA but caused a decrease in the level of NT-3 mRNA. All three TGF-beta m RNAs were detected in the maxillary territory in vivo before the arriv al of the earliest axons and their levels rose throughout the period i n which sensory axons reach this territory. Our findings demonstrate a ge-related changes in the influence of TGF-beta s on the expression of neurotrophins in developing cutaneous cells and raise the possibility that TGF-beta s play a role in regulating the changing patterns of ne urotrophin gene expression in sensory neuron target fields.