| First Author | Hesse K | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 8 | Pages | e23483 |
| PubMed ID | 21858141 | Mgi Jnum | J:177585 |
| Mgi Id | MGI:5295521 | Doi | 10.1371/journal.pone.0023483 |
| Citation | Hesse K, et al. (2011) AP-2delta is a crucial transcriptional regulator of the posterior midbrain. PLoS One 6(8):e23483 |
| abstractText | Ap-2 transcription factors comprise a family of 5 closely related sequence-specific DNA binding proteins that play pivotal and non-redundant roles in embryonic organogenesis. To investigate the function of Ap-2delta, wdeltae analyzed its expression during embryogenesis and generated Ap-2delta-deficient mice. In line with the specific expression pattern of Ap-2delta in the mesencephalic tectum and the dorsal midbrain, Ap-2delta-deficient mice failed to maintain the colliculus inferior, a derivative of the dorsal midbrain, as a consequence of increased apoptotic cell death. To identify specific Ap-2delta target genes in cells of the developing dorsal midbrain, we performed whole genome analysis of cDNA expression levels. This approach identified a set of 12 putative target genes being expressed in the developing midbrain, including the transcription factors Pitx2, Mef2c, Bhlhb4 and Pou4f3. Using chromatin immunoprecipitation (CHIP) we showed that some of these genes are direct targets of Ap-2delta. Consistently, we demonstrate that Ap-2delta occupies and activates the Pou4f3 and Bhlhb4 promoters. In addition, known Pou4f3 target genes were downregulated in the posterior midbrain of Ap-2delta-deficient mice. Despite the absence of a central part of the auditory pathway, the presence of neuronal responses to sounds in the neocortex of Ap-2delta-deficient mice indicates that auditory information from the brainstem still reaches the neocortex. In summary, our data define Ap-2delta as an important transcription factor, specifying gene expression patterns required for the development of the posterior midbrain. |
