The C terminus of p73 is essential for hippocampal development

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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
6 Downloads (Pure)

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 (Trp73 Δ13/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, Trp73 Δ13/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.
Original languageEnglish
Pages (from-to)15694-15701
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America (PNAS)
Volume117
Issue number27
Early online date22 Jun 2020
DOIs
Publication statusPublished - 7 Jul 2020

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