Neurotrophin Responsiveness is Differentially Regulatedin Neurons and Precursors Isolatedfrom the Developing Striatum

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Abstract
Sequential exposure to members of the neurotrophin family, nerve growth factor (NGF), neurotrophin-type 3 (NT3), brain-derived neurotrophic factor (BDNF), and neurotrophin-type 4 (NT4), determines the generation, survival, and maturation of developing neurons. The effects of neurotrophins depend on the stage of development and the target cell population. However, the nature of the responding cells is often unclear. In this study neurotrophin responsiveness was analyzed in murine embryonic striatal precursors and neurons. Individual neurotrophin-responsive cells were identified based on activation of intracellular signaling pathways to the transcription factor CREB and were further characterized using differentiation-stage specific markers. A dramatic developmentally regulated decrease in BDNF responsiveness was observed: BDNF targeted more than 40% of striatal neurons at E14 but only 12% at E18. The percentage of NT3-responsive neurons also moderately decreased during development while no change was observed in the fraction of neuronal cells targeted by NT4 and NGF. A different type of developmental change was found in striatal precursors. BDNF, NT3, and NT4 each targeted about 15% of striatal precursors at E14 but no NGF responsive-precursors were detected at this age. In contrast, only NT3 and NGF could induce a response in precursor cells at E18. NGF-responsive precursors shared a distinct morphology with a large cell body and high levels of nestin expression. These results indicate that during striatal development, the regulation of neurotrophin responsiveness is different in neurons and precursor cells.