DeltaNp73 regulates neuronal survival in vivo.
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.
Tissir
Fadel
F
Université catholique de Louvain, Institute of Neuroscience, Developmental Neurobiology Unit, Brussels, Belgium. fadel.tissir@uclouvain.be
Ravni
Aurélia
A
Achouri
Younès
Y
Riethmacher
Dieter
D
Meyer
Gundela
G
Goffinet
Andre M
AM
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000091042:Reelin Protein; C454920:delta Np73, mouse; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases