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The Journal of Neuroscience, January 15, 2001, 21(2):541-549
Defects in Sensory Axon Growth Precede Neuronal Death
in Brn3a-Deficient Mice
S. Raisa
Eng1,
Kevin
Gratwick1,
Jerry M.
Rhee1,
Natalia
Fedtsova1,
Lin
Gan3, and
Eric E.
Turner1, 2
1 Department of Psychiatry and 2 Program in
Neuroscience, University of California, San Diego and San Diego
Veterans Affairs Medical Center, La Jolla, California 92093 and
3 Center for Aging and Developmental Biology, University of
Rochester, Rochester, New York 14642
Brn3a/Brn-3.0 is a POU-domain transcription factor expressed in
primary sensory neurons of the cranial and dorsal root ganglia and in
specific neurons in the caudal CNS. Mice lacking Brn3a undergo
extensive sensory neural death late in gestation and die at birth. To
further examine Brn3a expression and the abnormalities that accompany
its absence, we constructed a transgene containing 11 kb of Brn3a
upstream regulatory sequence linked to a LacZ reporter. Here we show
that these regulatory sequences direct transgene expression
specifically to Brn3a peripheral sensory neurons of the cranial and
dorsal root ganglia. Furthermore, expression of the 11 kb/LacZ reporter
in the sensory neurons of the mesencephalic trigeminal, but not other
Brn3a midbrain neurons, demonstrates that cell-specific transgene
expression is targeted to a functional class of neurons rather than to
an anatomical region. We then interbred the 11 kb/LacZ reporter strain
with mice carrying a null mutant allele of Brn3a to generate 11 kb/LacZ, Brn3a knock-out mice.  -Galactosidase expression in these
mice reveals significant axonal growth defects, including excessive and
premature branching of the major divisions of the trigeminal nerve and
a failure to correctly innervate whisker follicles, all of which
precede sensory neural death in these mice. These defects in
Brn3a / mice resemble strongly those seen in mice
lacking the mediators of sensory pathfinding semaphorin 3A and
neuropilin-1. Here we show, however, that sensory neurons are able to
express neuropilin-1 in the absence of Brn3a.
Key words:
POU-domain; homeodomain; Brn3; TrkC; trigeminal ganglion; sensory ganglion; axon guidance
Copyright © 2001 Society for Neuroscience 0270-6474/01/212541-09$05.00/0
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