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DeltaNp73 regulates neuronal survival in vivo.

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Tissir, Fadel [UCL] Ravni, Aurélia [UCL] Achouri, Younes [UCL] Riethmacher, Dieter Meyer, Gundela Goffinet, André [UCL]

Apoptosis occurs widely during brain development, and p73 transcription factors are thought to play essential roles in this process. The p73 transcription factors are present in two forms, the full length TAp73 and the N-terminally truncated DeltaNp73. In cultured sympathetic neurons, overexpression of DeltaNp73 inhibits apoptosis induced by nerve growth factor withdrawal or p53 overexpression. To probe the function of DeltaNp73 in vivo, we generated a null allele and inserted sequences encoding the recombinase Cre and green fluorescent protein (EGFP). We show that DeltaNp73 is heavily expressed in the thalamic eminence (TE) that contributes neurons to ventral forebrain, in vomeronasal neurons, Cajal-Retzius cells (CRc), and choroid plexuses. In DeltaNp73(-/-) mice, cells in preoptic areas, vomeronasal neurons, GnRH-positive cells, and CRc were severely reduced in number, and choroid plexuses were atrophic. This phenotype was enhanced when DeltaNp73-positive cells were ablated by diphtheria toxin expression. However, ablation of cells that express DeltaNp73 and Wnt3a did neither remove all CRc, nor did they abolish Reelin secretion or generate a reeler-like cortical phenotype. Our data emphasize the role of DeltaNp73 in neuronal survival in vivo and in choroid plexus development, the importance of the TE as a source of neurons in ventral forebrain, and the multiple origins of CRc, with redundant production of Reelin.

Document type Article de périodique (Journal article) – Article de recherche – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès libre
Publication date 2009
Language Anglais
Journal information "Proceedings of the National Academy of Sciences of the United States of America" - Vol. 106, no. 39, p. 16871-6 (2009)
Peer reviewed yes
issn 0027-8424
e-issn 1091-6490
Publication status Publié
Affiliations UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
UCL - MD/BICL - Département de biochimie et de biologie cellulaire
MESH Subject Serine Endopeptidases - genetics - metabolism ; Nuclear Proteins - genetics - metabolism ; Neurons - metabolism ; Nerve Tissue Proteins - genetics - metabolism ; Mutation ; Mice ; Extracellular Matrix Proteins - genetics - metabolism ; Cell Survival ; Cell Death ; Cell Adhesion Molecules, Neuronal - genetics - metabolism ; Animals
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Bibliographic reference Tissir, Fadel ; Ravni, Aurélia ; Achouri, Younes ; Riethmacher, Dieter ; Meyer, Gundela ; et. al. DeltaNp73 regulates neuronal survival in vivo.. In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, no. 39, p. 16871-6 (2009)
Permanent URL http://hdl.handle.net/2078.1/24987