 |
 Previous Article | Next Article 
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
This article has been cited by other articles:
|
|
|
|
 
J. Hjerling-Leffler, F. Marmigere, M. Heglind, A. Cederberg, M. Koltzenburg, S. Enerback, and P. Ernfors
The boundary cap: a source of neural crest stem cells that generate multiple sensory neuron subtypes
Development,
June 1, 2005;
132(11):
2623 - 2632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Hudson, P. J. Morris, D. S. Latchman, and V. S. Budhram-Mahadeo
Brn-3a Transcription Factor Blocks p53-mediated Activation of Proapoptotic Target Genes Noxa and Bax in Vitro and in Vivo to Determine Cell Fate
J. Biol. Chem.,
March 25, 2005;
280(12):
11851 - 11858.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pan, Z. Yang, L. Feng, and L. Gan
Functional equivalence of Brn3 POU-domain transcription factors in mouse retinal neurogenesis
Development,
February 15, 2005;
132(4):
703 - 712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Wiggins, G. Wei, E. Doxakis, C. Wong, A. A. Tang, K. Zang, E. J. Luo, R. L. Neve, L. F. Reichardt, and E. J. Huang
Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival
J. Cell Biol.,
October 25, 2004;
167(2):
257 - 267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Eng, J. Lanier, N. Fedtsova, and E. E. Turner
Coordinated regulation of gene expression by Brn3a in developing sensory ganglia
Development,
August 15, 2004;
131(16):
3859 - 3870.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Li, F. Qiu, A. Xu, S. M. Price, and M. Xiang
Barhl1 Regulates Migration and Survival of Cerebellar Granule Cells by Controlling Expression of the Neurotrophin-3 Gene
J. Neurosci.,
March 24, 2004;
24(12):
3104 - 3114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Kimura-Yoshida, K. Kitajima, I. Oda-Ishii, E Tian, M. Suzuki, M. Yamamoto, T. Suzuki, M. Kobayashi, S. Aizawa, and I. Matsuo
Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarily conserved genetic mechanisms for vertebrate head specification
Development,
January 1, 2004;
131(1):
57 - 71.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Ma, L. Lei, S. R. Eng, E. Turner, and L. F. Parada
Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons
Development,
August 1, 2003;
130(15):
3525 - 3534.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. W. Wang, X. Mu, W. J. Bowers, D.-S. Kim, D. J. Plas, M. C. Crair, H. J. Federoff, L. Gan, and W. H. Klein
Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth
Development,
March 3, 2003;
129(2):
467 - 477.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Trieu, A. Ma, S. R. Eng, N. Fedtsova, and E. E. Turner
Direct autoregulation and gene dosage compensation by POU-domain transcription factor Brn3a
Development,
January 1, 2003;
130(1):
111 - 121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Perez-Sanchez, V. S. Budhram-Mahadeo, and D. S. Latchman
Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter
Nucleic Acids Res.,
November 15, 2002;
30(22):
4872 - 4880.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
