| First Author | Zhang SF | Year | 2022 |
| Journal | Stem Cell Reports | Volume | 17 |
| Issue | 9 | Pages | 2064-2080 |
| PubMed ID | 35931079 | Mgi Jnum | J:328995 |
| Mgi Id | MGI:7341135 | Doi | 10.1016/j.stemcr.2022.07.004 |
| Citation | Zhang SF, et al. (2022) The epigenetic state of EED-Gli3-Gli1 regulatory axis controls embryonic cortical neurogenesis. Stem Cell Reports 17(9):2064-2080 |
| abstractText | Mutations in the embryonic ectoderm development (EED) cause Weaver syndrome, but whether and how EED affects embryonic brain development remains elusive. Here, we generated a mouse model in which Eed was deleted in the forebrain to investigate the role of EED. We found that deletion of Eed decreased the number of upper-layer neurons but not deeper-layer neurons starting at E16.5. Transcriptomic and genomic occupancy analyses revealed that the epigenetic states of a group of cortical neurogenesis-related genes were altered in Eed knockout forebrains, followed by a decrease of H3K27me3 and an increase of H3K27ac marks within the promoter regions. The switching of H3K27me3 to H3K27ac modification promoted the recruitment of RNA-Pol2, thereby enhancing its expression level. The small molecule activator SAG or Ptch1 knockout for activating Hedgehog signaling can partially rescue aberrant cortical neurogenesis. Taken together, we proposed a novel EED-Gli3-Gli1 regulatory axis that is critical for embryonic brain development. |
