Senescence is a developmental mechanism that contributes to embryonic growth and patterning.
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.
Centre for Genomic Regulation (CRG) and UPF, Barcelona 08003, Spain.
Mekayla
M
Storer
Alba
A
Mas
Alexandre
A
Robert-Moreno
Matteo
M
Pecoraro
M Carmen
MC
Ortells
Valeria
V
Di Giacomo
Reut
R
Yosef
Noam
N
Pilpel
Valery
V
Krizhanovsky
James
J
Sharpe
William M
WM
Keyes
D000818:Animals; D017209:Apoptosis; D016922:Cellular Senescence; D002642:Chick Embryo; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D047108:Embryonic Development; D005121:Extremities / Q000196:embryology; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D051379:Mice; D019899:Paracrine Communication
D050762:Cyclin-Dependent Kinase Inhibitor p15; D050759:Cyclin-Dependent Kinase Inhibitor p21