Combinatorial Expression of Brn3 Transcription Factors in Somatosensory Neurons: Genetic and Morphologic Analysis

Abstract

The three members of the Brn3 family of POU-domain transcription factors (Brn3a/Pou4f1, Brn3b/Pou4f2, and Brn3c/Pou4f3) are expressed in overlapping subsets of visual, auditory/vestibular, and somatosensory neurons. Using unmarkedBrn3-null alleles andBrn3conditional alleles in which gene loss is coupled to expression of an alkaline phosphatase reporter, together with sparse Cre-mediated recombination, we describe the following: (1) the overlapping patterns ofBrn3gene expression in somatosensory neurons; (2) the manner in which these patterns correlate with molecular markers, peripheral afferent arbor morphologies, and dorsal horn projections; and (3) the consequences for these neurons of deleting individualBrn3genes in the mouse. We observe broad expression ofBrn3aamong DRG neurons, but subtype-restricted expression ofBrn3bandBrn3c. We also observe a nearly complete loss of hair follicle-associated sensory endings amongBrn3a^−/−neurons. Together with earlier analyses ofBrn3gene expression patterns in the retina and inner ear, these experiments suggest a deep functional similarity among primary somatosensory neurons, spiral and vestibular ganglion neurons, and retinal ganglion cells. This work also demonstrates the utility of sparse genetically directed labeling for visualizing individual somatosensory afferent arbors and for defining cell-autonomous mutant phenotypes.