title: Developmental roles of p73 in Cajal-Retzius cells and cortical patterning.
abstract: To examine the role of the p53 homolog p73 in brain development, we studied p73-/-, p73+/-, E2F1-/-, and reeler mutant mice. p73 in developing brain is expressed in Cajal-Retzius (CR) cells, the cortical hem, and the choroid plexus. p73-expressing CR cells are lost in p73-/- embryos, although Reelin is faintly expressed in the marginal zone. Ectopic neurons in the p73-/- preplate and cortical hem at embryonic day 12 implicate p73 in the early developmental program of the cortex; however, preplate partition and early cortical plate formation are not disturbed. Postnatal p73-/- mice show a mild hypoplasia of the rostral cortex and a severely disrupted architecture of the posterior telencephalon. In the developing p73-/- hippocampus, the most striking abnormality is the absence of the hippocampal fissure, suggesting a role of p73 in cortical folding. p73+/- mice have a less severe cortical phenotype; they display a dorsal shift of the entorhinal cortex and a reduced size of occipital and posterior temporal areas, which acquire entorhinal-like features such as Reelin-positive cells in layer II. CR cells appear unaffected by heterozygosity. We relate the malformations of the posterior pole in p73 mutant mice to alterations of p73 expression in the cortical hem and suggest that p73 forms part of an early signaling network that controls neocortical and archicortical regionalization. In mice deficient for the transcription factor E2F1, a main activator of the TAp73 (transactivating p73) isoform, we find a defect of the caudal cortical architecture resembling the p73+/- phenotype along with reduced TAp73 protein levels and propose that an E2F1-TAp73 dependent pathway is involved in cortical patterning.
authors.affiliation: Department of Anatomy, University La Laguna, 38071 La Laguna, Tenerife, Spain. gmeyer@ull.es
authors.forename: Gundela
authors.initials: G
authors.lastname: Meyer
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cabrera Socorro
authors.forename: Carlos Gustavo
authors.initials: CG
authors.lastname: Perez Garcia
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez Millan
authors.forename: Nancy
authors.initials: N
authors.lastname: Walker
authors.forename: Daniel
authors.initials: D
authors.lastname: Caput
mesh_terms: D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000196:embryology* / Q000254:growth & development*; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D002540:Cerebral Cortex / Q000002:abnormalities / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D016147:Genes, Tumor Suppressor; D008032:Limbic System / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D020033:Protein Isoforms / Q000502:physiology; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D000091042:Reelin Protein; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C454920:delta Np73, mouse; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases