DeltaNp73 regulates neuronal survival in vivo

Fadel Tissir, Aurélia Ravni, Younès Achouri, Dieter Riethmacher, Gundela Meyer, Andre M. Goffinet

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)16871-16876
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number39
DOIs
Publication statusPublished - Sep 29 2009
Externally publishedYes

Fingerprint

Choroid Plexus
Neurons
Prosencephalon
Transcription Factors
Apoptosis
Phenotype
Diphtheria Toxin
Preoptic Area
Nerve Growth Factor
Green Fluorescent Proteins
Gonadotropin-Releasing Hormone
Alleles
Brain

Keywords

  • Cajal-Retzius cells
  • P73
  • Reelin
  • Thalamic eminence
  • Vomeronasal nerve

ASJC Scopus subject areas

  • General

Cite this

DeltaNp73 regulates neuronal survival in vivo. / Tissir, Fadel; Ravni, Aurélia; Achouri, Younès; Riethmacher, Dieter; Meyer, Gundela; Goffinet, Andre M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 39, 29.09.2009, p. 16871-16876.

Research output: Contribution to journalArticle

Tissir, Fadel ; Ravni, Aurélia ; Achouri, Younès ; Riethmacher, Dieter ; Meyer, Gundela ; Goffinet, Andre M. / DeltaNp73 regulates neuronal survival in vivo. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 39. pp. 16871-16876.
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