Serotonin limits generation of chromaffin cells during adrenal organ development

• Published in: Nature communications 2022-05, Vol.13 (1), p.2901-2901, Article 2901
• Main Authors: Kameneva, Polina, Melnikova, Victoria I., Kastriti, Maria Eleni, Kurtova, Anastasia, Kryukov, Emil, Murtazina, Aliia, Faure, Louis, Poverennaya, Irina, Artemov, Artem V., Kalinina, Tatiana S., Kudryashov, Nikita V., Bader, Michael, Skoda, Jan, Chlapek, Petr, Curylova, Lucie, Sourada, Lukas, Neradil, Jakub, Tesarova, Marketa, Pasqualetti, Massimo, Gaspar, Patricia, Yakushov, Vasily D., Sheftel, Boris I., Zikmund, Tomas, Kaiser, Jozef, Fried, Kaj, Alenina, Natalia, Voronezhskaya, Elena E., Adameyko, Igor
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 38/32; 38/91; 631/136; 631/136/2086; 631/378/1457; 631/67/2332; 692/163; Adaptation; Adrenal glands; Adrenal Glands - metabolism; Animals; Catecholamines; Catecholamines - metabolism; Cell cycle; Cell lines; Cell number; Chromaffin cells; Chromaffin Cells - metabolism; Embryos; Female; Fetuses; Hormones; Humanities and Social Sciences; Maternal effects; Medicin och hälsovetenskap; Mice; multidisciplinary; Neuroblastoma; Neuroblastoma - metabolism; Offspring; Organs; Pregnancy; Progenitor cells; Progeny; Prolongation; Rodents; Science; Science (multidisciplinary); Serotonin; Serotonin - metabolism; Stress response; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30438-w

Adrenal glands are the major organs releasing catecholamines and regulating our stress response. The mechanisms balancing generation of adrenergic chromaffin cells and protecting against neuroblastoma tumors are still enigmatic. Here we revealed that serotonin (5HT) controls the numbers of chromaffin cells by acting upon their immediate progenitor “bridge” cells via 5-hydroxytryptamine receptor 3A (HTR3A), and the aggressive HTR3A high human neuroblastoma cell lines reduce proliferation in response to HTR3A-specific agonists. In embryos (in vivo), the physiological increase of 5HT caused a prolongation of the cell cycle in “bridge” progenitors leading to a smaller chromaffin population and changing the balance of hormones and behavioral patterns in adulthood. These behavioral effects and smaller adrenals were mirrored in the progeny of pregnant female mice subjected to experimental stress, suggesting a maternal-fetal link that controls developmental adaptations. Finally, these results corresponded to a size-distribution of adrenals found in wild rodents with different coping strategies. Adrenal glands are major organs regulating stress response., Melnikova et al., show that local release of serotonin limits adrenalin-producing cell number during rodent development, a mechanism which has implications for neuroblastoma development and stress-related maternal effects transmitted to progeny.