TY - JOUR
T1 - XSenescence is a developmental mechanism that contributes to embryonic growth and patterning
AU - Storer, Mekayla
AU - Mas, Alba
AU - Robert-Moreno, Alexandre
AU - Pecoraro, Matteo
AU - Ortells, M. Carmen
AU - Di Giacomo, Valeria
AU - Yosef, Reut
AU - Pilpel, Noam
AU - Krizhanovsky, Valery
AU - Sharpe, James
AU - Keyes, William M.
N1 - La Caixa fellowship; Spanish Ministry; Plan Nacional grant; Spanish Ministry for Science and Innovation [SAF2010-18829]; CRG core fundingWe are grateful to the CRG genomics, histology, and mouse facilities for technical help, Manuela Hummel for bioinformatics analysis, Juan Valcarcel for helpful discussions, Juan-Martin Caballero for mouse models, and Juan Jose Sanz and Jelena Raspopovic for technical advice. In addition, we thank Manuel Serrano for sharing unpublished data, technical assistance, and submission coordination. M. S. and V. D. G. are funded by "La Caixa'' fellowships, and M. P. by an FPI fellowship from the Spanish Ministry. This work was funded in part by a Plan Nacional grant to W.M.K. from the Spanish Ministry for Science and Innovation (SAF2010-18829) and CRG core funding.
PY - 2013/11/21
Y1 - 2013/11/21
N2 - Senescence is a form of cell-cycle arrest linked to tumor suppression and aging. However, it remains controversial and has not been documented in nonpathologic states. Here we describe senescence as a normal developmental mechanism found throughout the embryo, including the apical ectodermal ridge (AER) and the neural roof plate, two signaling centers in embryonic patterning. Embryonic senescent cells are nonproliferative and share features with oncogene-induced senescence (OIS), including expression of p21, p15, and mediators of the senescence-associated secretory phenotype (SASP). Interestingly, mice deficient in p21 have defects in embryonic senescence, AER maintenance, and patterning. Surprisingly, the underlying mesenchyme was identified as a source for senescence instruction in the AER, whereas the ultimate fate of these senescent cells is apoptosis and macrophage-mediated clearance. We propose that senescence is a normal programmed mechanism that plays instructive roles in development, and that OIS is an evolutionarily adapted reactivation of a developmental process.
AB - Senescence is a form of cell-cycle arrest linked to tumor suppression and aging. However, it remains controversial and has not been documented in nonpathologic states. Here we describe senescence as a normal developmental mechanism found throughout the embryo, including the apical ectodermal ridge (AER) and the neural roof plate, two signaling centers in embryonic patterning. Embryonic senescent cells are nonproliferative and share features with oncogene-induced senescence (OIS), including expression of p21, p15, and mediators of the senescence-associated secretory phenotype (SASP). Interestingly, mice deficient in p21 have defects in embryonic senescence, AER maintenance, and patterning. Surprisingly, the underlying mesenchyme was identified as a source for senescence instruction in the AER, whereas the ultimate fate of these senescent cells is apoptosis and macrophage-mediated clearance. We propose that senescence is a normal programmed mechanism that plays instructive roles in development, and that OIS is an evolutionarily adapted reactivation of a developmental process.
UR - http://www.scopus.com/inward/record.url?scp=84889565689&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cell.2013.10.041
DO - https://doi.org/10.1016/j.cell.2013.10.041
M3 - مقالة
SN - 0092-8674
VL - 155
SP - 1119
JO - Cell
JF - Cell
IS - 5
ER -