Role of transforming growth factor-beta isoforms in regulating the expression of nerve growth factor and neurotrophin-3 mRNA levels in embryonic cutaneous cells at different stages of development.

We have investigated if transforming growth factor-beta (TGF-beta) isoforms influence the level of expression of nerve growth factor (NGF) mRNA and neurotrophin-3 (NT-3) mRNA in embryonic tissues innervated by neurons that depend on NGF and NT-3 for survival. Presumptive dermal and 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 dependence from NT-3 to NGF. In E11 and E12 cultures, when the in vivo levels 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 and NT-3 mRNA reach a peak (relative to actin mRNA) prior to a marked fall in the level of NT-3 mRNA and a gradual decrease in the level of NGF 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 mRNAs were detected in the maxillary territory in vivo before the arrival of the earliest axons and their levels rose throughout the period in which sensory axons reach this territory.(ABSTRACT TRUNCATED AT 250 WORDS)