Regulation of the Serotonin Neuron Fate in Stem Cells by foxa2 and shh

The central serotonergic system is comprised of tryptophan hydroxylase-expressing neurons located in the raphe nuclei of the brain stem. Rostral groups of raphe serotonin neurons project throughout the forebrain, while caudal groups innervate the brain stem and spinal cord [1]. The serotonergic system modulates mood [2], anxiety [3], aggression [4], reward systems [5], and impulsivity [6], and psychosis [7]. Many psychiatric diseases, such as depression, obsessive-compulsive disorder, and bulimia nervosa are currently treated by medications targeting the serotonergic system [8,9]. Abnormalities in the serotonergic system have also been implicated in diseases affecting early development such as sudden infant death syndrome [10] and autism [11]. Recent evidence suggests that dysregulation of serotonin neuron development may underlie behavioral changes. The activity of 5HT1A receptor during postnatal development has been shown to be important for normal anxiety behavior in adult mice [12]. The loss of Pet-1, a transcription factor important for the development of serotonin neurons in the embryo has been shown to cause increased anxiety and aggression in adult mice [13]. A more precise understanding of the development of the serotonergic system may be critical for understanding the relationship between early changes in serotonergic regulation and the pathophysiology of psychiatric disorders, autism, and sudden infant death syndrome.