| First Author | Amelio I | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 27 | Pages | 15694-15701 |
| PubMed ID | 32571922 | Mgi Jnum | J:291525 |
| Mgi Id | MGI:6444558 | Doi | 10.1073/pnas.2000917117 |
| Citation | Amelio I, et al. (2020) The C terminus of p73 is essential for hippocampal development. Proc Natl Acad Sci U S A 117(27):15694-15701 |
| abstractText | The p53 family member p73 has a complex gene structure, including alternative promoters and alternative splicing of the 3' UTR. This results in a complex range of isoforms whose biological relevance largely remains to be determined. By deleting exon 13 (which encodes a sterile alpha motif) from the Trp73 gene, we selectively engineered mice to replace the most abundantly expressed C-terminal isoform, p73alpha, with a shorter product of alternative splicing, p73beta. These mice (Trp73 (Delta13/Delta13) ) display severe neurodevelopmental defects with significant functional and morphological abnormalities. Replacement of p73alpha with p73beta results in the depletion of Cajal-Retzius (CR) cells in embryonic stages, thus depriving the developing hippocampus of the pool of neurons necessary for correct hippocampal architecture. Consequently, Trp73 (Delta13/Delta13) mice display severe hippocampal dysgenesis, reduced synaptic functionality and impaired learning and memory capabilities. Our data shed light on the relevance of p73 alternative splicing and show that the full-length C terminus of p73 is essential for hippocampal development. |
