The C terminus of p73 is essential for hippocampal development

Morone, Nobuhiro; Amelio, Ivano; Panatta, Emanuele; Niklison-Chirou, Maria Victoria; Steinert, Joern R.; Agostini, Massimiliano; Melino, Gerry; Knight, Richard A.

Abstract

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 α motif) from the Trp73 gene, we selectively engineered mice to replace the most abundantly expressed C-terminal isoform, p73α, with a shorter product of alternative splicing, p73β. These mice (Trp73Δ13/Δ13) display severe neurodevelopmental defects with significant functional and morphological abnormalities. Replacement of p73α with p73β 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, Trp73Δ13/Δ13 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.

Citation

Morone, N., Amelio, I., Panatta, E., Niklison-Chirou, M. V., Steinert, J. R., Agostini, M., …Knight, R. A. (2020). The C terminus of p73 is essential for hippocampal development. Proceedings of the National Academy of Sciences, 117(27), 15694-15701. https://doi.org/10.1073/pnas.2000917117

• Journal Article Type: Article
• Acceptance Date: May 28, 2020
• Online Publication Date: Jun 22, 2020
• Publication Date: Jul 7, 2020
• Deposit Date: Jun 23, 2020
• Publicly Available Date: Jun 23, 2020
• Journal: Proceedings of the National Academy of Sciences
• Print ISSN: 0027-8424
• Electronic ISSN: 1091-6490
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 117
• Issue: 27
• Pages: 15694-15701
• DOI: https://doi.org/10.1073/pnas.2000917117
• Keywords: Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/4704780
• Publisher URL: https://www.pnas.org/content/early/2020/06/19/2000917117