AP-2δ is a crucial transcriptional regulator of the posterior midbrain.
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-2δ, wδe analyzed its expression during embryogenesis and generated Ap-2δ-deficient mice. In...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858141/?tool=EBI |
| _version_ | 1818717185907884032 |
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| author | Katrin Hesse Kristina Vaupel Simone Kurt Reinhard Buettner Jutta Kirfel Markus Moser |
| author_facet | Katrin Hesse Kristina Vaupel Simone Kurt Reinhard Buettner Jutta Kirfel Markus Moser |
| author_sort | Katrin Hesse |
| collection | DOAJ |
| description | 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-2δ, wδe analyzed its expression during embryogenesis and generated Ap-2δ-deficient mice. In line with the specific expression pattern of Ap-2δ in the mesencephalic tectum and the dorsal midbrain, Ap-2δ-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-2δ 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-2δ. Consistently, we demonstrate that Ap-2δ occupies and activates the Pou4f3 and Bhlhb4 promoters. In addition, known Pou4f3 target genes were downregulated in the posterior midbrain of Ap-2δ-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-2δ-deficient mice indicates that auditory information from the brainstem still reaches the neocortex. In summary, our data define Ap-2δ as an important transcription factor, specifying gene expression patterns required for the development of the posterior midbrain. |
| first_indexed | 2024-12-17T19:31:08Z |
| format | Article |
| id | doaj.art-27fcdf15c2cf4c5db9262971dab71d3f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T19:31:08Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-27fcdf15c2cf4c5db9262971dab71d3f2022-12-21T21:35:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2348310.1371/journal.pone.0023483AP-2δ is a crucial transcriptional regulator of the posterior midbrain.Katrin HesseKristina VaupelSimone KurtReinhard BuettnerJutta KirfelMarkus MoserAp-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-2δ, wδe analyzed its expression during embryogenesis and generated Ap-2δ-deficient mice. In line with the specific expression pattern of Ap-2δ in the mesencephalic tectum and the dorsal midbrain, Ap-2δ-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-2δ 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-2δ. Consistently, we demonstrate that Ap-2δ occupies and activates the Pou4f3 and Bhlhb4 promoters. In addition, known Pou4f3 target genes were downregulated in the posterior midbrain of Ap-2δ-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-2δ-deficient mice indicates that auditory information from the brainstem still reaches the neocortex. In summary, our data define Ap-2δ as an important transcription factor, specifying gene expression patterns required for the development of the posterior midbrain.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858141/?tool=EBI |
| spellingShingle | Katrin Hesse Kristina Vaupel Simone Kurt Reinhard Buettner Jutta Kirfel Markus Moser AP-2δ is a crucial transcriptional regulator of the posterior midbrain. PLoS ONE |
| title | AP-2δ is a crucial transcriptional regulator of the posterior midbrain. |
| title_full | AP-2δ is a crucial transcriptional regulator of the posterior midbrain. |
| title_fullStr | AP-2δ is a crucial transcriptional regulator of the posterior midbrain. |
| title_full_unstemmed | AP-2δ is a crucial transcriptional regulator of the posterior midbrain. |
| title_short | AP-2δ is a crucial transcriptional regulator of the posterior midbrain. |
| title_sort | ap 2δ is a crucial transcriptional regulator of the posterior midbrain |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858141/?tool=EBI |
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