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.


CONCLUSIONS
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.
Eng
S Raisa
SR
Department of Psychiatry, University of California, San Diego and VA San Diego Healthcare System, Gilman Drive, La Jolla, CA 92093-0603, USA. sreng@ucsd.edu
Dykes
Iain M
IM
Lanier
Jason
J
Fedtsova
Natalia
N
Turner
Eric E
EE
D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004475:Ectoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020868:Gene Silencing / Q000502:physiology; D006657:Histones / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D050819:Transcription Factor Brn-3A / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D006657:Histones; C494189:Pou4f1 protein, mouse; D050819:Transcription Factor Brn-3A