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

Brn3a/Brn-3.0 is a POU-domain transcription factor expressed in primary sen sory neurons of the cranial and dorsal root ganglia and in specific neurons in the caudal CNS. Mice lacking Brn3a undergo extensive sensory neural dea th late in gestation and die at birth. To further examine Brn3a expression and the abnormalities that accompany its absence, we constructed a transgen e containing 11 kb of Brn3a upstream regulatory sequence linked to a LacZ r eporter. Here we show that these regulatory sequences direct transgene expr ession 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 mi dbrain neurons, demonstrates that cell-specific transgene expression is tar geted 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. beta - Galactosidase expression in these mice reveals significant axonal growth de fects, including excessive and premature branching of the major divisions o f the trigeminal nerve and a failure to correctly innervate whisker follicl es, all of which precede sensory neural death in these mice. These defects in Brn3a2/2 mice resemble strongly those seen in mice lacking the mediators of sensory pathfinding semaphorin 3A and neuropilin-1. Here we show, howev er, that sensory neurons are able to express neuropilin-1 in the absence of Brn3a.