Developmental regulation of brain-derived neurotrophic factor messenger RNAs transcribed from different promoters in...

During the development of the nervous system many types of neurons are produced in excess and die because they fail to obtain sufficient amounts of target-derived neurotrophic factors (for review, see Refs 1, 16). Brain-derived neurotrophic factor is a protein that belongs to the nerve growth factor family of neurotrophins (for review, see Ref. 17) which promotes the survival and differentiation of distinct neuronal populations that partially overlap with those affected by the other members of the family (for review, see Ref. 11). We have recently shown that four promoters direct tissue specific expression of the rat brain-derived neurotrophic factor gene. In the present study we have quantified the levels of brain-derived neurotrophic factor messenger RNAs transcribed from different promoters during the rat brain development. Our data show that different promoters have specific regulation patterns during embryonic development but are regulated coordinately in several regions of rat brain during postnatal development, suggesting that the four transcription units have both distinct and common regulatory elements. Quantification of absolute levels of brain-derived neurotrophic factor messenger RNA revealed that it is expressed significantly higher in the rat brain than previously estimated.