TRANSGENIC ANALYSES REVEAL DEVELOPMENTALLY-REGULATED NEURON-SPECIFIC AND MUSCLE-SPECIFIC ELEMENTS IN THE MURINE NEUROFILAMENT LIGHT-CHAIN GENE PROMOTER

We report here the developmental activity of regula tory elements that reside within 1.7 kilobases of the murine neurofilament light chain ( NF-L) gene promoter. NF-L promoter activity is first detected at embry onic day 8.5 in neuroepithelial cells. Neuron specific gene expression is maintained in the spinal cord until embryonic day 12.5 and at late r developmental stages in the brain and sensory neuroepithelia. After day 14.5, the promoter becomes active in myogenic cells. Transgene exp ression in both neurons and muscle is consistent with the detection of endogenous NF-L transcript in both neuronal and myogenic tissues of n eonates by reverse transcriptase-polymerase chain reaction. Neuron- an d muscle-specific activities of the NF-L promoter decrease and are nea rly undetectable after birth. Thus, the 1.7-kilobase NF-L promoter con tains regulatory elements for initiation but not maintenance of transc ription from the NF-L locus. Deletion analyses reveal that independent regulatory elements control the observed tissue-specific activities a nd implicate a potential MyoD binding site as the muscle-specific enha ncer. Our results demonstrate that the NF-L promoter contains distinct regulatory elements for both neuron-and muscle-specific gene expressi on and that these activities are temporally separated during embryogen esis.