TGFβ2-induced senescence during early inner ear development

• Published in: Scientific reports Vol. 9; no. 1; p. 5912
• Main Authors: Gibaja, Alejandro, Aburto, María R., Pulido, Sara, Collado, Manuel, Hurle, Juan M., Varela-Nieto, Isabel, Magariños, Marta
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.04.2019; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/2; 13/51; 13/95; 14; 14/1; 14/19; 14/63; 38; 38/77; 631/378/2571; 631/80/509; 64/60; 82/29; 96/21; Aging; Animals; Apoptosis; Autophagy; Cancer; Cell Differentiation; Cellular Senescence; Chickens; Ear, Inner - growth & development; Ear, Inner - metabolism; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Embryogenesis; Gene Expression Regulation, Developmental; Growth factors; Humanities and Social Sciences; Inner ear; Insulin; Insulin-like growth factor I; Mice; Morphogenesis; multidisciplinary; Organogenesis; Phagocytosis; Science; Science (multidisciplinary); Senescence; Signal Transduction; Transforming Growth Factor beta2 - genetics; Transforming Growth Factor beta2 - metabolism; Transforming growth factor-b
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-42040-0

Embryonic development requires the coordinated regulation of apoptosis, survival, autophagy, proliferation and differentiation programs. Senescence has recently joined the cellular processes required to master development, in addition to its well-described roles in cancer and ageing. Here, we show that senescent cells are present in a highly regulated temporal pattern in the developing vertebrate inner ear, first, surrounding the otic pore and, later, in the otocyst at the endolymphatic duct. Cellular senescence is associated with areas of increased apoptosis and reduced proliferation consistent with the induction of the process when the endolymphatic duct is being formed. Modulation of senescence disrupts otic vesicle morphology. Transforming growth factor beta (TGFβ) signaling interacts with signaling pathways elicited by insulin-like growth factor type 1 (IGF-1) to jointly coordinate cellular dynamics required for morphogenesis and differentiation. Taken together, these results show that senescence is a natural occurring process essential for early inner ear development.