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Journal of Neuroscience, Vol 15, 4762-4785, Copyright © 1995 by Society for Neuroscience
The Brn-3 family of POU-domain factors: primary structure, binding specificity, and expression in subsets of retinal ganglion cells and somatosensory neurons
M Xiang, L Zhou, JP Macke, T Yoshioka, SH Hendry, RL Eddy, TB Shows and J Nathans
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
A search for POU domain sequences expressed in the human retina has led to
the identification of three closely related genes: Brn-3a, Brn-3b, and
Brn-3c. The structure and expression pattern of Brn-3b was reported earlier
(Xiang et al., 1993); we report here the structures and expression patterns
of Brn-3a and Brn-3c. Antibodies specific for each Brn-3 protein were
generated and shown to label only ganglion cells in a variety of vertebrate
retinas. A complex pattern of strongly and weakly immunolabeled ganglion
cells was observed in mouse, cat, and monkey retinae. In mouse and cat
retinae, Brn-3a and Brn-3b proteins are found in a large fraction of
ganglion cells, whereas Brn-3c is present in fewer ganglion cells. In the
cat retina, anti-Brn-3a immunoreactivity was strong in the small ganglion
cells (gamma cells) and weak in the remaining ganglion cells (alpha and
beta cells); anti- Brn-3b immunoreactivity was present in all ganglion
cells; and anti- Brn3c immunoreactivity was confined to the small ganglion
cells. Immunolabeling of macaque retinae following retrograde labeling from
the lateral geniculate nucleus revealed strong anti-Brn-3a immunoreactivity
in a minority of retrogradely labeled P-type ganglion cells, and weak
Brn-3a immunoreactivity in all of the remaining P- and M-type ganglion
cells. In the same retinae, strong anti-Brn-3b immunoreactivity was seen in
nearly all P-type ganglion cells and weak immunoreactivity in nearly all
M-type ganglion cells. Each of the Brn-3- specific antibodies also labeled
subsets of neurons in the dorsal root and trigeminal ganglia, suggesting
that primary somatosensory neurons and retinal ganglion cells share genetic
regulatory hierarchies. In vitro selection of an optimal DNA binding site
using the Brn-3b POU domain has revealed a consensus [(A/G)CTCATTAA(T/C)]
that is recognized by each of the Brn-3 POU domains and is distinct from
binding sites previously described for other POU domain proteins.
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