Transport mechanisms for serotonin

Researchers at The Forsyth Institute have discovered that the transport mechanisms for serotonin - the chemical substance involved in transmitting signals between neurons, and which has a role in anxiety and mood disorders - play a key role in determining where organs are positioned in the body during embryonic development. Transporters bring serotonin into cells.

The research team, led by Dr. Michael Levin, found that when the transport of serotonin into cells was blocked, normal development was disrupted in frog and chick embryos.

In particular, left-right asymmetry, the process through which cells "know" which side they are on as they form body organs such as the heart and liver, is controlled by serotonin transporters. Michael Levin, PhD., Associate Member of the Staff, conducted his research with substances commonly used to treat mood disorders in humans including the drug Prozac. These drugs address chemical imbalances in the brain by blocking serotonin's removal from the space between neurons.

"With this research, we've not only identified a novel role of the serotonin transporters, in contributing to left-right asymmetry, but have also confirmed that serotonin has a role in cells other than neurons," Levin said. "This raises interesting questions related to embryonic development and also about the possible subtle side-effects of serotonin-related drugs like the selective serotonin reuptake inhibitors (SSRI antidepressants such as Prozac and Zoloft) or the monoamine oxidase inhibitors (MAOIs)."

This study, published in the most recent issue of Developmental Neuroscience, has ramifications for neuroscience, developmental genetics, evolutionary biology and, possibly teratology (a branch of pathology and embryology concerned with abnormal development and congenital malformations).

In previous studies, Dr. Levin found that frog embryos contain a supply of serotonin provided in the egg by the mother. This maternal serotonin functions during the first few cell divisions and then is degraded by an enzyme, monoamine oxidase, which has many important functions in human neurobiology. Chick embryos, on the other hand, synthesize their own serotonin shortly after fertilization. Though details differ, both species utilize serotonin signaling as a patterning mechanism long before the appearance of the nervous system, suggesting that this novel role for serotonin signaling may be conserved in a number of different species.

While the previous study demonstrated the importance of serotonin receptors, which sense serotonin present outside cells, the latest work showed that the transport of serotonin into cells is also crucial. This highlights the importance of dynamic serotonin movement as part of cellular cross-talk, and also suggests that there are important functions for serotonin inside of cells about which we know very little. The future characterization of these internal serotonin targets represents an exciting and fruitful area for basic biology and drug development.

Michael Levin, Ph.D. is Associate Member of the Staff, is an Associate Member of the Staff in The Forsyth Institute Department of Cytokine Biology. Through experimental approaches and mathematical modeling, Dr. Levin and his team examine the processes governing large-scale pattern formation and biological information storage during embryonic development. The lab's investigations are directed toward understanding the mechanisms of signaling between cells and tissues that allows a biological system to reliably generate and maintain a complex morphology. The Levin team studies these processes in the context of embryonic development and regeneration, with a particular focus on the biophysics of cell behavior.