Developmental Roles of p73 in Cajal-Retzius Cells and Cortical Patterning
| Autor: | Alfredo Cabrera Socorro, Gundela Meyer, Carlos Gustavo Perez Garcia, Nancy Walker, Daniel Caput, Luis Martinez Millan |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cell Adhesion Molecules
Neuronal Development/Plasticity/Repair Cell Cycle Proteins Nerve Tissue Proteins Mice Mice Neurologic Mutants Limbic system Reeler Limbic System medicine Animals Protein Isoforms Genes Tumor Suppressor Reelin skin and connective tissue diseases neoplasms Cerebral Cortex Mice Knockout Neurons Extracellular Matrix Proteins biology Cerebrum Tumor Suppressor Proteins General Neuroscience Serine Endopeptidases Brain Nuclear Proteins Tumor Protein p73 Entorhinal cortex Marginal zone E2F Transcription Factors DNA-Binding Proteins Mice Inbred C57BL Reelin Protein Phenotype medicine.anatomical_structure Cerebral cortex biology.protein Choroid plexus Neuroscience E2F1 Transcription Factor Transcription Factors |
| Zdroj: | The Journal of Neuroscience. 24:9878-9887 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | To examine the role of the p53 homolog p73 in brain development, we studiedp73-/-,p73+/-,E2F1-/-, andreelermutant 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 inp73-/-embryos, although Reelin is faintly expressed in the marginal zone. Ectopic neurons in thep73-/-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. Postnatalp73-/-mice show a mild hypoplasia of the rostral cortex and a severely disrupted architecture of the posterior telencephalon. In the developingp73-/-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 thep73+/-phenotype along with reduced TAp73 protein levels and propose that an E2F1-TAp73 dependent pathway is involved in cortical patterning. |
| Databáze: | OpenAIRE |
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