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: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:The chromatin remodeler BRG1 is altered in the Letmd1 KO mice. We performed chromatin IP for BRG1 from BAT of wild-type (WT) versus Letmd1 KO mice.
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: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.