Serotonin limits generation of chromaffin cells during adrenal organ development

Abstract

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 HTR3Ahigh 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.

MOXD1 is a gate-keeper of organ homeostasis and functions as a tumor-suppressor in neuroblastoma

“…NB is believed to form following disrupted trunk NC (tNC) cell (tNCC) differentiation; however, the NB founder cell type is still unknown. Lately, many efforts have been made to map the cellular composition of normal developing human and murine adrenal medulla with single cell RNA sequencing (scRNA seq) to the features of NB cells (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Findings show that NB cells relate to various stages during normal neuroblast maturation.…”

Inhibiting mitochondrial translation overcomes multidrug resistance in MYC-driven neuroblastoma via OMA1-mediated integrated stress response

“…RNA isolation, reverse transcription and qPCR were performed as previously described [76]. The list of primer sequences used is provided in Supplementary Table 5.…”

What made us “hunter-gatherers of words”

“…Specifically, Kameneva et al (2022) posit that chromaffin cell number (and adrenal gland size) control via serotonin-sensitive precursor (co-called "bridge") cells, which also express GRIK3 and CADPS2 already mentioned above, "may provide a regulatory serotonin-mediated pathway of prenatal programming for long-lasting changes in progeny underlying the behavior of domesticated species as well as wild animals with active and reactive types of coping strategy." As Kameneva et al (2022) note, "[a]ggressive males typically express a more proactive type of behavioral response demonstrating rigid, cue-independent, and impulsive reactions and a tendency to defend their home territory. .…”

“…Behavioral phenotypes similar to those associated with CADM2 -variation (impulsivity, risk-taking behavior) mentioned above are also reported with variation linked to serotonin, another neurotransmitter frequently brought up in domestication studies (Wang et al, 2018 ). Specifically, Kameneva et al ( 2022 ) posit that chromaffin cell number (and adrenal gland size) control via serotonin-sensitive precursor (co-called “bridge”) cells, which also express GRIK3 and CADPS2 already mentioned above, “may provide a regulatory serotonin-mediated pathway of prenatal programming for long-lasting changes in progeny underlying the behavior of domesticated species as well as wild animals with active and reactive types of coping strategy.” As Kameneva et al ( 2022 ) note, “[a]ggressive males typically express a more proactive type of behavioral response demonstrating rigid, cue-independent, and impulsive reactions and a tendency to defend their home territory. …Non-aggressive reactive males are rather flexible, cautious, and open to the external cues, which can assist in variable or unpredictable environments.”…”