Defects in sensory axon growth precede neuronal death in Brn3a-deficient mice

S. Raisa Eng, Kevin Gratwick, Jerry M. Rhee, Natalia Fedtsova, Lin Gan, Eric E. Turner

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79 Scopus citations

Abstract

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 knockout mice. β-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.

Original languageEnglish (US)
Pages (from-to)541-549
Number of pages9
JournalJournal of Neuroscience
Volume21
Issue number2
StatePublished - Jan 15 2001
Externally publishedYes

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Keywords

  • Axon guidance
  • Brn3
  • Homeodomain
  • POU-domain
  • Sensory ganglion
  • Trigeminal ganglion
  • TrkC

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Raisa Eng, S., Gratwick, K., Rhee, J. M., Fedtsova, N., Gan, L., & Turner, E. E. (2001). Defects in sensory axon growth precede neuronal death in Brn3a-deficient mice. Journal of Neuroscience, 21(2), 541-549.