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Título
p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
Autor
Facultad/Centro
Área de conocimiento
Título de la revista
Cell Death & Disease
Datos de la obra
González-Cano, L., Herreros-Villanueva, M., Fernández-Alonso, R., Ayuso-Sacido, A., Meyer, G., García-Verdugo, J. M., Silva, A., Marqués, M. M. and Marín, M. C. (2010). p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53. Cell Death & Disease, 1, Article e109. https://doi.org/10.1038/cddis.2010.87
Editor
Springer Nature
Fecha
2010
Abstract
[EN] The question of how neural progenitor cells maintain its self-renewal throughout life is a fundamental problem in cell biology with implications in cancer, aging and neurodegenerative diseases. In this work, we have analyzed the p73 function in embryonic neural progenitor cell biology using the neurosphere (NS)-assay and showed that p73-loss has a significant role in the maintenance of neurosphere-forming cells in the embryonic brain. A comparative study of NS from Trp73-/-, p53KO, p53KO;Trp73-/- and their wild-type counterparts demonstrated that p73 deficiency results in two independent, but related, phenotypes: a smaller NS size (related to the proliferation and survival of the neural-progenitors) and a decreased capacity to form NS (self-renewal). The former seems to be the result of p53 compensatory activity, whereas the latter is p53 independent. We also demonstrate that p73 deficiency increases the population of neuronal progenitors ready to differentiate into neurons at the expense of depleting the pool of undifferentiated neurosphere-forming cells. Analysis of the neurogenic niches demonstrated that p73-loss depletes the number of neural-progenitor cells, rendering deficient niches in the adult mice. Altogether, our study identifies TP73 as a positive regulator of self-renewal with a role in the maintenance of the neurogenic capacity. Thus, proposing p73 as an important player in the development of neurodegenerative diseases and a potential therapeutic target
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ID proyecto
- info:eu-repo/grantAgreement/MICINN/Programa Nacional de Investigación Fundamental/SAF2009-07897/ES/Identificación de las funciones del gen TP73 en la biología de las células troncales hematopoyéticas y neurales
- info:eu-repo/grantAgreement/Junta de Castilla y León//LE015A10-2/fiEstudio de las funciones coordinadas de los supresores tumorales TP73 y TP53 en la biología de las células troncales neurales y su relevancia en envejecimiento y enfermedades neurodegenerativasfl
- info:eu-repo/grantAgreement/Junta de Castilla y León//LE030A07/Análisis de la inhibición funcional de los miembros de la familia de p53 en células madre embrionarias murinas: efectos sobre la diferenciación y la respuesta al daño genotóxico
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