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Conserved and distinct regulatory targets of Brn3a at different levels of the sensory axis

ABSTRACT: 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. 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 downstream gene expression, but a subset of genes show increased expression only at cranial levels. Although silent in wild-type ganglia, the promoter regions of genes which are activated in the absence of Brn3a also exhibit increased histone H3-acetylation at levels similar to constitutively transcribed gene loci, and this H3-acetylation is tissue-specific for genes which are increased only in the TG. 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. Keywords: Gene expression in the developing nervous system

ORGANISM(S): Mus musculus

PROVIDER: GSE5658 | GEO | 2007/01/28

SECONDARY ACCESSION(S): PRJNA96867

REPOSITORIES: GEO

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Project description:Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. In order to elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488 conjugated Cholera toxin B allowed identification of neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser capture microdissection. Gene expression profiles of visceral afferent neurons, obtained by microarray hybridization, were analysed using multivariate spectral map analysis, SAM algorithm (Significance Analysis of Microarray data) and fold-difference filtering. A total of 1996 genes were found to be differentially expressed in DRG versus NG, including 41 G-protein coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, a detailed catalogue of all adrenergic and cholinergic, GABA, glutamate, serotonin and dopamine receptors, voltage-gated potassium, sodium and calcium channels and transient receptor potential cation channels present in visceral afferents is provided. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG visceral sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacologic agents modulating visceral sensation. Experiment Overall Design: Three separate experiments were performed. First, 5 whole dorsal root ganglia were compared to 7 whole nodose ganglia. Second, Laser captured visceral neurons derived from 5 dorsal root ganglia and 5 nodose ganglia were compared on MG-U74Av2. Third, Laser captured visceral neurons derived from 9 dorsal root ganglia and 11 nodose ganglia were compared on Mouse430_2.

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Conserved and distinct regulatory targets of Brn3a at different levels of the sensory axis

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