RT info:eu-repo/semantics/article
T1 p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
A1 González Cano, Laura
A1 Herreros Villanueva, Marta
A1 Fernández Alonso, Rosalía
A1 Ayuso Sacido, Ángel
A1 Meyer, Gundela
A1 García Verdugo, José Manuel 1954-
A1 Silva, Augusto G.
A1 Marqués Martínez, Margarita
A1 Marín Vieira, María Carmen
A2 Biologia Celular
K1 Biología
K1 Medicina. Salud
K1 Differentiation
K1 Neural stem cells
K1 p73
K1 p53
K1 Self-renewal
K1 Asymmetric division
K1 2407 Biología Celular
K1 2407.02 Citogenética
K1 3207.11 Neuropatología
AB [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
PB Springer Nature
LK https://hdl.handle.net/10612/20939
UL https://hdl.handle.net/10612/20939
NO 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
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 27-jun-2024