Expression profile of P7 control and Lhx2 cKO somatosensory cortex
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE92372 | GEO | 2016/12/15
SECONDARY ACCESSION(S): PRJNA357362
REPOSITORIES: GEO
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Project description:Lhx2 is a retinal progenitor cell transcription factor critical for eye development. We previously reported that conditional inactivation of Lhx2 at the start of mouse retinal neurogenesis disrupted retinal progenitor cell (RPC) proliferation, greatly reduced the RPC pool and altered neurogenic output as indicated by changes in the production of multiple fated precursor populations. To identify genes whose expression levels are dependent on Lhx2 at this stage of development, Lhx2 conditional inactivation was initiated at E11.5 in RPCs with the progenitor Cre driver Hes1CreERT2 and retinal tissue was collected at E15.5 for RNA sequencing. The gene expression profiles of Lhx2 CKO retinas were compared to control (Lhx2 conditional heterozygotes) were compared. Downregulated and upregulated gene expression was observed, with some likely due to direct and indirect regulation by Lhx2 within RPCs and others due to changes in differentiation and the altered neurogenic output.
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Project description:Expression profile of P7 control and Lhx2 cKO somatosensory cortex
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Project description:To investigate the gene program activated by serotonergic hallucinogens in mouse somatosensory cortex, the effects of the 5-HT2A agonist (±)2,5-dimethoxy 4-iodoamphetamine (DOI) on gene expression was studied. The 5-HT2A serotonin receptor is a member of the 5-HT2 receptor subfamily of G protein–coupled receptors. The 5-HT2A receptor is thought to modulate processes related to cognition, appetite, mood, anxiety, sleep, and sexual behavior. Abnormal function of this receptor has been implicated in neuropsychiatric disorders such as major depression and schizophrenia. In particular, the 5-HT2A receptor has been implicated in the modulation of the mechanisms related to psychosis. We compared gene response patterns in the somatosensory cortical brain area, which has a high density of 5-HT2A receptors and has been implicated in the action of hallucinogenic drugs. Mice (strain 129Sv) were injected with DOI (2 mg/kg or 10 mg/kg) or vehicle, animals were sacrificed after 1 h, and somatosensory cortex samples dissected on ice for RNA extraction. Seven independent microarray hybridizations from seven different DOI- or vehicle-treated mouse pairs were performed. Keywords: other
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Project description:Expression of the lim-homeodomain transcription factor is required for sustained maintenance of heamatopoietic stem cell like cells in undifferentiated form durng in vitro culturing. Cell lines were created from the mouse embryonic stem (ES) cell line, Ainv15. The gene Lhx2 was introducted into these cells under the control of a tetracycline-responsive element. In the presence of tetracycline (or its analogue doxycycline), these cells express Lhx2. In DoxHPC7 GFP is co-expressed together with the Lhx2 gene. We used these cells to carry out a time-course study where the effects of Lhx2 withdrawal were studied.
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Project description:The Lhx2 transcription factor plays essential roles in morphogenesis and patterning of ectodermal derivatives, as well as in controlling stem cell activity. Lhx2 is expressed in the hair follicle (HF) buds, while in postnatal telogen HFs Lhx2+ cells reside in the stem cell-enriched epithelial compartments (bulge, secondary hair germ) and co-express selected stem cell markers (Sox9, Tcf4 and Lgr5). Lhx2+ cells represent the vast majority of cells in the bulge and secondary hair germ that proliferate in response to skin injury. This is functionally important, since the wound re-epithelialization is significantly retarded in heterozygous Lhx2 knockout (+/-) mice, while anagen onset in the HFs located closely to the wound is accelerated compared to wild-type mice. Cell proliferation in the bulge and the number of Sox9+ and Tcf4+ cells in the HFs closely adjacent to the wound in Lhx2+/- mice are decreased in comparison to wild-type controls, while expression of Lgr5 and cell proliferation in the secondary hair germ are increased. Furthermore, acceleration of wound-induced anagen development in Lhx2+/- mice is inhibited by administration of Lgr5 siRNA. In addition, Chip-on-chip/ChIP-qPCR and reporter assay analyses reveal Sox9, Tcf4 and Lgr5 as direct Lhx2 targets in keratinocytes. These data strongly suggest that Lhx2 positively regulates Sox9 and Tcf4 in the bulge cells and promotes wound re-epithelization, while it simultaneously negatively regulates Lgr5 in the secondary hair germ and inhibits HF cycling. Thus, Lhx2 operates as a regulator of epithelial stem cell activity during skin response to injury. Chromatin form primary mouse keratinocytes (PMK) was subjected to ChIP analysis with Lhx2 antibody; input and ChIP DNA were labelled with Cy3 and Cy5 respectivly and used form Nimblegen MM8 Mouse Promoter Array
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