POU-domain factor Brn3a regulates both distinct and common programs of gene expression in the spinal and trigeminal sensory ganglia

BACKGROUND: General somatic sensation is conveyed to the central nervous system at cranial levels by the trigeminal ganglion (TG), and at spinal levels by the dorsal root ganglia (DRG). Although these ganglia have similar functions, they have distinct embryological origins, in that both contain neurons originating from the neural crest, while only the TG includes cells derived from the placodal ectoderm. RESULTS: Here we use microarray analysis of E13.5 embryos to demonstrate that the developing DRG and TG have very similar overall patterns of gene expression. In mice lacking the POU-domain transcription factor Brn3a, the DRG and TG exhibit many common changes in gene expression, but a subset of Brn3a target genes show increased expression only in the TG. In the wild-type TG these Brn3a-repressed genes are silent, yet their promoter regions exhibit histone H3-acetylation levels similar to constitutively transcribed gene loci. This increased H3-acetylation is not observed in the DRG, suggesting that chromatin modifications play a role in cell-specific target gene regulation by Brn3a. CONCLUSION: These results demonstrate that one developmental role of Brn3a is to repress potential differences in gene expression between sensory neurons generated at different axial levels, and to regulate a convergent program of developmental gene expression, in which functionally similar populations of neurons are generated from different embryological substrates

Regulation of the development of tectal neurons and their projections by transcription factors Brn3a and Pax7

AbstractThe rostral part of the dorsal midbrain, known as the superior colliculus in mammals or the optic tectum in birds, receives a substantial retinal input and plays a diverse and important role in sensorimotor integration. However, little is known about the development of specific subtypes of neurons in the tectum, particularly those which contribute tectofugal projections to the thalamus, isthmic region, and hindbrain. Here we show that two homeodomain transcription factors, Brn3a and Pax7, are expressed in mutually exclusive patterns in the developing and mature avian midbrain. Neurons expressing these factors are generated at characteristic developmental times, and have specific laminar fates within the tectum. In mice expressing βgalactosidase targeted to the Pou4f1 (Brn3a) locus, Brn3a-expressing neurons contribute to the ipsilateral but not the contralateral tectofugal projections to the hindbrain. Using misexpression of Brn3a and Pax7 by electroporation in the chick tectum, combined with GFP reporters, we show that Brn3a determines the laminar fate of subsets of tectal neurons. Furthermore, Brn3a regulates the development of neurons contributing to specific ascending and descending tectofugal pathways, while Pax7 globally represses the development of tectofugal projections to nearly all brain structures

Placodal Origin of Brn-3—Expressing Cranial Sensory Neurons

The Brn-3 class of POU-domain transcription factors includes three genes in mammals which have key roles in the development of specific groups of sensory neurons. Here, we have identified three avian genes which correspond to the murine genes Brn-3.0, Brn-3.1, and Brn-3.2. Using an in situ hybridization probe generic for this gene class, the earliest detectable expression of Brn-3 in the chick is at stage 15, in placodal and migrating precursors of the trigeminal ganglion. By stage 19, Brn-3.0 protein is detectable in the trigeminal and vestibulocochlear ganglia with Brn-3.0-specific antisera, and Brn-3 message expression has extended to the dorsal root ganglia. At later stages, when condensation of the trigeminal ganglion is complete, Brn-3.0-immunoreactive neurons are concentrated in the portion of the ganglion distal to the brain stem. To examine the developmental origin of the Brn-3 expressing cells, we combined lipophilic dye (DiI) labeling with in situ hybridization. DiI labeling of the placodal surface ectoderm and of premigratory neural crest cells in the neural tube reveals that all, or nearly all, of the Brn-3-expressing neurons in the trigeminal ganglia are derived from the sensory placodes and not from the neural crest, and thus, that Brn-3 is an early marker of the placode-derived sensory neural lineage