M. Behrens et al., NFI in the development of the olfactory neuroepithelium and the regulationof olfactory marker protein gene expression., EUR J NEURO, 12(4), 2000, pp. 1372-1384
Nuclear factor I (NFI) proteins are DNA-binding transcription factors that
participate in the tissue specific expression of various genes. They are en
coded by four different genes (NFI-A, B, C, and X) each of which generates
multiple isoforms by alternative RNA splicing. NFI-like binding sites have
been identified in several genes preferentially expressed in olfactory rece
ptor neurons. Our prior demonstration that NFI binds to these elements led
to the hypothesis that NFI is involved in the regulation of these genes. To
analyse the role of NFI in the regulation of olfactory neuron gene express
ion we have performed transient transfection experiments in HEK 293 cells u
sing constructs that place luciferase expression under the control of an ol
factory marker protein (OMP)-promoter fragment containing the NFI binding s
ite. In vitro mutagenesis of this site revealed a negative modulation of lu
ciferase expression by endogenous NFI proteins in HEK 293 cells. In additio
n, we have used in situ hybridization to analyse the tissue and cellular di
stribution of the four NFI gene transcripts during pre- and postnatal mouse
development. We have simultaneously characterized the expression of Pax-6,
and O/E-1, transcription factors known to regulate the phenotype of olfact
ory receptor neurons. We demonstrate that all of these transcription factor
s vary in specific spatio-temporal patterns during the development of the o
lfactory system. These data on NFI activity, and on transcription factor ex
pression, provide a basis to understand the role of NFI in regulating gene
expression in olfactory receptor neurons.