Coordinated regulation of gene expression by Brn3a in developing sensory ganglia
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE3895 | GEO | 2005/12/24
SECONDARY ACCESSION(S): PRJNA94143
REPOSITORIES: GEO
Similar Datasets
Project description:Mice lacking the POU-domain transcription factor Brn3a exhibit marked defects in sensory axon growth and abnormal sensory apoptosis. We have determined the regulatory targets of Brn3a in the developing trigeminal ganglion using microarray analysis of Brn3a mutant mice. These results show that Brn3 mediates the coordinated expression of neurotransmitter systems, ion channels, structural components of axons and inter- and intracellular signaling systems. Loss of Brn3a also results in the ectopic expression of transcription factors normally detected in earlier developmental stages and in other areas of the nervous system. Target gene expression is normal in heterozygous mice, consistent with prior work showing that autoregulation by Brn3a results in gene dosage compensation. Detailed examination of the expression of several of these downstream genes reveals that the regulatory role of Brn3a in the trigeminal ganglion appears to be conserved in more posterior sensory ganglia but not in the CNS neurons that express this factor. Experiment Overall Design: Microarrays used to compare the patterns of gene expression in the trigeminal ganglia of Brn3a knockout and wild-type mice. Embryonic day 13.5 (E13.5) was chosen because at this point in development mutant mice exhibit major defects in sensory axon growth, but have yet to undergo the period of extensive sensory neuron death associated with later stages.
2007-11-01 | E-GEOD-3895 | biostudies-arrayexpress
Project description: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. Experiment Overall Design: Microarrays used to compare the patterns of gene expression in the dorsal root ganglia and trigeminal ganglia of Brn3a knockout and wild-type mice. Embryonic day 13.5 (E13.5) was chosen because at this point in development mutant mice exhibit major defects in sensory axon growth, but have yet to undergo the period of extensive sensory neuron death associated with later stages.
2008-06-14 | E-GEOD-5658 | biostudies-arrayexpress
Project description: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
2007-01-28 | GSE5658 | GEO
Project description:The sense of taste starts with activation of receptor cells in taste buds by chemical stimuli which then communicate this signal via innervating oral sensory neurons to the CNS. The cell bodies of oral sensory neurons reside in the geniculate ganglion (GG) and nodose/petrosal/jugular ganglion. The geniculate ganglion contains two main neuronal populations, BRN3A+ somatosensory neurons that innervate the pinna, and PHOX2B+ sensory neurons that innervate the oral cavity. While much is known about the different taste bud cell subtypes, much less is known about the molecular identities of PHOX2B+ sensory subpopulations. In the GG as many as 12 different subpopulations have been predicted from electrophysiological studies, while transcriptional identities exist for only 3-6. Importantly, the cell fate pathways that diversify PHOX2B+ oral sensory neurons into these subpopulations are unknown. The transcription factor EGR4 was identified as being highly expressed in GG neurons. EGR4 deletion causes GG oral sensory neurons to lose their expression of PHOX2B and other oral sensory genes, and upregulate BRN3A. This is followed by a severe loss of chemosensory innervation of taste buds, a loss of Type II taste cells responsive to bitter, sweet, and umami stimuli, and a concomitant increase in Type I glial-like taste bud cells. These deficits culminate in a loss of nerve responses to sweet and umami taste qualities. Taken together, we identify a critical role of EGR4 in cell fate specification and maintenance of subpopulations of GG neurons, which in turn maintain the appropriate sweet and umami taste receptor cells.
2023-02-01 | GSE223724 | GEO
Project description:Using targeted gene deletion, we have firmly established that the Class IV POU domain transcription factor Brn-3.2 controls a developmental program regulating axon pathfinding in the mouse visual system. We have isolated and identified downstream gene targets of Brn-3.2, using Representational Difference Analysis (RDA), on cDNA populations derived from wildtype and Brn-3.2-/- retina at the appropriate embryonic stage. One of these candidate genes, the Homeodomain Interacting Protein Kinase 2 (HIPK2), is postulated to be a transcriptional coregulator, based on its in vitro interactions with repressor homeodomain proteins of the NK class, as well as other components of repressor complexes. HIPK2 has also been shown to be involved in post-translational modification of two major transcriptional regulators, p53 and CtBP. Expression of a dominant-negative form of HIPK2 in sensory neurons affects the innervation patterns of their target tissues, suggesting an axon pathfinding defect.,The aim of this project is to identify targets for the Homeodomain Interacting Protein Kinase 2 (HIPK2), that we isolated as a downstream gene target of the class IV POU domain transcription factor Brn-3.2, and to investigate their function in the Brn-3.2 dependent pathway regulating axon pathfinding. ,We hypothesize that the genes regulated by HIPK2 will play a critical role in axon pathfinding and that the results of this study will provide novel insights into the molecular mechanisms of axon pathfinding, and possibly neural plasticity and regeneration, and therefore, be of great interest to the field of neurobiology in general.,In order to uncover potential biological role(s) of HIPK2 in neural development, and particularly axon pathfinding, we generated transgenic mouse models for in vivo studies. Our preliminary observations in transgenic mice, indicate that a form of the molecule expected to act as a dominant-negative and designed to be expressed in sensory neurons, affects the innervation patterns of their target tissues, suggesting an axon pathfinding defect. We plan to take advantage of this model to identify genes regulated by HIPK2, and which are likely to be involved in axon pathfinding. To this end, we will compare gene expression profiles in sensory neurons isolated wild-type and transgenic mice. In our experimental paradigm, the trigeminal ganglion represents the ideal sensory structure in which to perform such an analysis: 1) High levels of transgene can be expressed in the trigeminal ganglion, as assessed by the expression of LacZ from the bicistronic construct which contains IRES-LacZ downstream of a dominant negative form of HIPK2. 2) The trigeminal ganglion can be dissected at embryonic day 13.5, when the phenotype is apparent, with ease and free of contamination from surrounding tissues. 3) The amounts of RNA that can be isolated from a single ganglion are in the range of 200-300 ng, which should be sufficient for microarray analysis following linear amplification of RNA. One series will be carried out with transgenic embryos and a control series will be carried out with wildtype littermates. Animals will be prepared and sacrificed by a standard protocol. Tissue will be rapidly dissected from E13.5 trigeminal ganglion, frozen in liquid nitrogen, and stored at -80C until RNA is extracted. RNA will be prepared using RNeasy Micro Kit. We will be providing 4 tissue samples for each of the wildtype and transgenic animals to mitigate any expression differences resulting from mouse to mouse variation.
2007-07-31 | E-GEOD-2869 | biostudies-arrayexpress
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals. Gene expression measurements implicate a TRPV1 splice isoform as the heat-sensitive channel in vampire bats
2011-08-04 | E-GEOD-28243 | biostudies-arrayexpress
Project description:Coordinated regulation of gene expression by Brn3a in developing sensory ganglia
| PRJNA94143 | ENA
Project description:Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli including touch, temperature, and pain to the central nervous system. Recent advances in single-cell RNA-sequencing (scRNA-seq) have provided new insights into the diversity of sensory ganglia cell types in rodents, non-human primates, and humans, but it remains difficult to compare transcriptomically defined cell types across studies and species. Here, we built cross-species harmonized atlases of DRG and TG cell types that describe 18 neuronal and 11 non-neuronal cell types across 6 species and 31 studies. We then demonstrate the utility of this harmonized reference atlas by using it to annotate newly profiled DRG nuclei/cells from both human and the highly regenerative axolotl. We observe that the transcriptomic profiles of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The new resources and data presented here can guide future studies in comparative transcriptomics, simplify cell type nomenclature differences across studies, and help prioritize targets for future analgesic development.
2024-07-29 | GSE255436 | GEO
Project description:The sensitization of trigeminal ganglion neurons contributes to primary headache disorders such as migraine, but the specific neuronal and non-neuronal trigeminal subtypes involved remain unclear. We thus developed a cell atlas in which human and mouse trigeminal ganglia are transcriptionally and epigenomically profiled at single-cell resolution. These data describe evolutionarily conserved and human-specific gene expression patterns within each trigeminal ganglion cell type, as well as the transcription factors and gene regulatory elements that contribute to cell-type-specific gene expression. We then leverage these data to identify trigeminal ganglion cell types that are implicated both by human genetic variation associated with migraine and two mouse models of headache. This trigeminal ganglion cell atlas improves our understanding of the cell types, genes, and epigenomic features involved in headache pathophysiology and establishes a rich resource of cell-type-specific molecular features to guide the development of more selective treatments for headache and facial pain.
2022-02-26 | GSE197289 | GEO
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals.
2011-08-04 | GSE28243 | GEO