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Transcription Factors Dlx1/2 Are Required for Making All Interneurons in the Olfactory Bulb [Pax6]

ABSTRACT: Purpose: To assess changes in gene expression profiles from the E16.5 wild type littermate controls cortex and Pax6 sey/sey mutant mice cortex. Methods: Total RNA was isolated and sequenced using an Illumina Hi-seq 2500. Raw data was analyzed using TopHat. Genes were considered significantly changed which perform P value <= 0.05. Results: Compared to controls, 173 genes were significantly down regulated, and 245 genes were up regulated in the RNA expression level of the mutant cortex.

ORGANISM(S): Mus musculus

PROVIDER: GSE121213 | GEO | 2019/01/25

REPOSITORIES: GEO

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Transcription Factors Dlx1/2 Are Required for Making All Interneurons in the Olfactory Bulb [Dlx1/2]

Project description:Purpose: To assess changes in gene expression profiles from the E16.5 wild type littermate controls LGE and Dlx1/2-/- mutant mice LGE (lateral ganglionic eminence). Methods: Total RNA was isolated and sequenced using an Illumina Hi-seq 2500. Raw data was analyzed using TopHat. Genes were considered significantly changed which perform fold-change>=2 and P value <= 0.05. Results: Compared to controls, 804 genes were significantly down regulated, and 673 genes were up regulated in the RNA expression level of the mutant LGE.

2019-01-25 | GSE121214 | GEO

Transcription Factors Dlx1/2 Are Required for Making All Interneurons in the Olfactory Bulb [Pax6]

Project description:Transcription Factors Dlx1/2 Are Required for Making All Interneurons in the Olfactory Bulb [Pax6]

| PRJNA496335 | ENA

Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons.

Project description:Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2F/- mice), GSX2+ and ASCL1+ neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1, and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development.

| S-EPMC6917526 | biostudies-literature

Transcription Factors Dlx1/2 Are Required for Making All Interneurons in the Olfactory Bulb [Dlx1/2]

Project description:Transcription Factors Dlx1/2 Are Required for Making All Interneurons in the Olfactory Bulb [Dlx1/2]

| PRJNA496340 | ENA

Dlx1/2 Are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons

Project description:Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2F/- mice), GSX2+ and ASCL1+ neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1 and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development. This SuperSeries is composed of the SubSeries listed below.

2019-01-24 | GSE121215 | GEO

Adult generation of glutamatergic olfactory bulb interneurons.

Project description:The adult mouse subependymal zone (SEZ) harbors neural stem cells that are thought to exclusively generate GABAergic interneurons of the olfactory bulb. We examined the adult generation of glutamatergic juxtaglomerular neurons, which had dendritic arborizations that projected into adjacent glomeruli, identifying them as short-axon cells. Fate mapping revealed that these originate from Neurog2- and Tbr2-expressing progenitors located in the dorsal region of the SEZ. Examination of the progenitors of these glutamatergic interneurons allowed us to determine the sequential expression of transcription factors in these cells that are thought to be hallmarks of glutamatergic neurogenesis in the developing cerebral cortex and adult hippocampus. Indeed, the molecular specification of these SEZ progenitors allowed for their recruitment into the cerebral cortex after a lesion was induced. Taken together, our data indicate that SEZ progenitors not only produce a population of adult-born glutamatergic juxtaglomerular neurons, but may also provide a previously unknown source of progenitors for endogenous repair.

| S-EPMC2787799 | biostudies-literature

Regulating lineage progression of cortical neural stem cells by extrinsic signaling molecule SHH [single-cell RNA-seq]

Project description:Purpose:To asses changes in gene expression profiles of single cell from the E16.5 wild type littermate controls cortex, and ShhN IUE (ShhN palsmid were electroporated to wild type mice cortex at E13.5 and the cortex were dissected at E16.5) mice. Methords: E16.5 wild type and ShhN-IUE cortices were carefully dissected under a fluorescent stereoscope, and incubated in 4 ml of papain solution for 20 min at 37℃, The cortical tissues were gently triturated, filtered through a 40 mm strainer, and washed with HBSS to obtain the single cell suspension. The Chromium droplet-based sequencing platform (10X Genomics) was used to generate scRNA-seq libraries, following the manufacturer’s instructions. The cDNA libraries were purified, quantified using Agilent 2100 Bioanalyzer, and sequenced on the Illumina Hiseq4000 Results: 7834 cells (2368 median genes per cell) captured for the Control cortex. And 8538 cells with 2422 median genes per cell captured for Shh-IUE mice.

2020-02-19 | GSE140816 | GEO

Parvalbumin-expressing interneurons linearly control olfactory bulb output.

Project description:In the olfactory bulb, odor representations by principal mitral cells are modulated by local inhibitory circuits. While dendrodendritic synapses between mitral and granule cells are typically thought to be a major source of this modulation, the contributions of other inhibitory neurons remain unclear. Here we demonstrate the functional properties of olfactory bulb parvalbumin-expressing interneurons (PV cells) and identify their important role in odor coding. Using paired recordings, we find that PV cells form reciprocal connections with the majority of nearby mitral cells, in contrast to the sparse connectivity between mitral and granule cells. In vivo calcium imaging in awake mice reveals that PV cells are broadly tuned to odors. Furthermore, selective PV cell inactivation enhances mitral cell responses in a linear fashion while maintaining mitral cell odor preferences. Thus, dense connections between mitral and PV cells underlie an inhibitory circuit poised to modulate the gain of olfactory bulb output.

| S-EPMC3884945 | biostudies-literature

Pax6 regulates Tbr1 and Tbr2 expressions in olfactory bulb mitral cells.

Project description:Tracking olfactory bulb mitral cell development with BrdU labeling, we find that mitral cells are generated from Pax6+ radial glial cells in the ventricular zone of the embryonic olfactory bulb. Unlike cortical projection neurons, postmitotic mitral cell precursors express both Tbr1 and Tbr2. Our tracking experiments revealed that down-regulation of Pax6 preceded up-regulation of Tbrs, and that Tbr1 emerged earlier than Tbr2. Using in utero electroporation, we also show that Pax6 negatively regulates the expression of Tbr1 and Tbr2 in postmitotic mitral cell precursors. Exogenous expression of Pax6 in embryonic olfactory bulb postmitotic precursors decreased the number of cells that progressed to a mitral cell fate. In contrast, exogenous expression of Pax6 resulted in an increase of GABAergic and/or dopaminergic interneurons. These results indicate that Pax6 is a regulator of fate determination of precursor cells.

| S-EPMC3622182 | biostudies-literature

Reduced conditioned fear response in mice that lack Dlx1 and show subtype-specific loss of interneurons.

Project description:UnlabelledThe inhibitory GABAergic system has been implicated in multiple neuropsychiatric diseases such as schizophrenia and autism. The Dlx homeobox transcription factor family is essential for development and function of GABAergic interneurons. Mice lacking the Dlx1 gene have postnatal subtype-specific loss of interneurons and reduced IPSCs in their cortex and hippocampus. To ascertain consequences of these changes in the GABAergic system, we performed a battery of behavioral assays on the Dlx1 mutant mice, including zero maze, open field, locomotor activity, food intake, rotarod, tail suspension, fear conditioning assays (context and trace), prepulse inhibition, and working memory related tasks (spontaneous alteration task and spatial working memory task). Dlx1 mutant mice displayed elevated activity levels in open field, locomotor activity, and tail suspension tests. These mice also showed deficits in contextual and trace fear conditioning, and possibly in prepulse inhibition. Their learning deficits were not global, as the mutant mice did not differ from the wild-type controls in tests of working memory. Our findings demonstrate a critical role for the Dlx1 gene, and likely the subclasses of interneurons that are affected by the lack of this gene, in behavioral inhibition and associative fear learning. These observations support the involvement of particular components of the GABAergic system in specific behavioral phenotypes related to complex neuropsychiatric diseases.Electronic supplementary materialThe online version of this article (doi:10.1007/s11689-009-9025-8) contains supplementary material, which is available to authorized users.

| S-EPMC2758250 | biostudies-literature

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