Project description:Slc39a8 KO mouse embryo hearts exhibit ventricle noncompaction phenotype which becomes evident at E12.5. The goal of this experiment is to identify genes that are differentially expressed between Slc39a8 KO and WT, which may be underlying the phenotype.
Project description:Neocortical projection neurons of mammalian brains are largely direct daughters of intermediate progenitors (IP), which are progenies of radial glial cells (RG). The maintenance of the RG pool, production and expansion of IPs are essential for neocortical formation during development, as well as neocortical expansion during evolution. Here we characterized an epigenetic circuit that controls precise neurogenic programming of the neocortex. The circuit comprises a long non-coding RNA – LncBAR and the SWI/SNF (BAF) chromatin-remodeling complex, which transcriptionally maintains the expression of Zbtb20. LncBAR knockout neocortex contains fewer upper-layer projection neurons. Intriguingly, loss of LncBAR promotes IP production of RGCs, but hampers neurogenic division and lengthens the cell-cycle durations of IPs during mid-later cortical neurogenesis. Moreover, in LncBAR knockout mice, depletion of the neural progenitor pool at embryonic stage causes fewer adult neural stem cells at the subventricular zone, leading to compromised adult neurogenesis to replenish the olfactory bulb. LncBAR binds to BRG1, the core enzymatic component of the SWI/SNF (BAF) chromatin-remodeling complex. LncBAR depletion enhances association of BRG1 with and the genomic locus of, and suppresses the expression of Zbtb20, a transcription factor gene known to regulate both embryonic and adult neurogenesis. ZBTB20 re-expression in LncBAR-knockout neural precursors reversed compromised neurogenic divisions of IPCs. Together, we revealed a previously unidentified epigenetic machinery to control neurogenesis of neural precursors.
Project description:Neocortical projection neurons of mammalian brains are largely direct daughters of intermediate progenitors (IP), which are progenies of radial glial cells (RG). The maintenance of the RG pool, production and expansion of IPs are essential for neocortical formation during development, as well as neocortical expansion during evolution. Here we characterized an epigenetic circuit that controls precise neurogenic programming of the neocortex. The circuit comprises a long non-coding RNA – LncBAR and the SWI/SNF (BAF) chromatin-remodeling complex, which transcriptionally maintains the expression of Zbtb20. LncBAR knockout neocortex contains fewer upper-layer projection neurons. Intriguingly, loss of LncBAR promotes IP production of RGCs, but hampers neurogenic division and lengthens the cell-cycle durations of IPs during mid-later cortical neurogenesis. Moreover, in LncBAR knockout mice, depletion of the neural progenitor pool at embryonic stage causes fewer adult neural stem cells at the subventricular zone, leading to compromised adult neurogenesis to replenish the olfactory bulb. LncBAR binds to BRG1, the core enzymatic component of the SWI/SNF (BAF) chromatin-remodeling complex. LncBAR depletion enhances association of BRG1 with and the genomic locus of, and suppresses the expression of Zbtb20, a transcription factor gene known to regulate both embryonic and adult neurogenesis. ZBTB20 re-expression in LncBAR-knockout neural precursors reversed compromised neurogenic divisions of IPCs. Together, we revealed a previously unidentified epigenetic machinery to control neurogenesis of neural precursors.
Project description:The cRNA derived from Brain and Gut neurospheres of wild type and BMI-1 knockout mice were hybridized to Affymetrix mouse ver 2 Chips A, B and C. In case of brain neurospheres, the cRNA were generated by one round RNA amplification (conventional method). In contrast, the cRNA of Gut neurospheres were generated by two round RNA amplifications. Keywords: parallel sample
Project description:E2F4 wild and knockout type neurospheres from E12.5 forebrain. E2F4 transcription factor regulates the expression of the genes which are required for neural stem cell expansion in the developing mouse brain. The results of microarray analysis will help to identify the signaling pathways affected by E2F4 deletion and refine the neural stem cell regulatory mechanism. Keywords: other
Project description:E2F4 wild and knockout type neurospheres from E12.5 forebrain. E2F4 transcription factor regulates the expression of the genes which are required for neural stem cell expansion in the developing mouse brain. The results of microarray analysis will help to identify the signaling pathways affected by E2F4 deletion and refine the neural stem cell regulatory mechanism. Experiment Overall Design: This experiment include 2 samples on 2 platforms for a total of 4 Samples.
Project description:Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin, colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial epigenetic regulator of neural development that controls histone acetylation and gene expression, thereby providing a likely explanation for its association with cognitive dysfunction and ASD. We used microarrays to compare the gene expression profile in embryonic neurospheres prepared from neocortices of WT and Ankrd11Yod/+ mice E14.5 cortical secondary neurosheres 5 days post-passage were collected and total RNA extracted. cDNA was hybridized on Affymetrix Mouse Gene 2.0 ST Array and gene expression was analyzed using Parterk software. In total, 6 Ankrd11Yod/+ and 5 WT embryos were used.