The Serotonin Transporter and the Vesicular Monoamine Transporters During Development

Abstract: In the present study, the mRNA encoding the serotonin transporter (5-HTT) and two isoforms of the vesicular monoamine transporters (VMAT1 and VMAT2) have been mapped in the rat throughout gestation and early postnatal development using in situ hybridization, RT PCR and immunohistochemistry. 5-HTT mRNA was found in serotonergic neurons and VMAT2 mRNA in all monoaminergic neurons from early gestation. A transient 5-HTT and VMAT2 mRNAs expression was also detected in thalamic neurons lacking tryptophan hydroxylase (TPH), the enzyme of 5-HT synthesis. VMAT1 mRNA was expressed in several limbic structures, cerebellum and the subventricular zone. In peripheral structures 5-HTT and both VMAT mRNAs were expressed in neural crest derived tissues such as autonomic and sensory ganglia. In addition, VMAT1 mRNA was expressed by organs of the endocrine system. Neuroepithelial cells were isolated from the snout and identified as Merkel cells. These cells exclusively expressed 5-HTT mRNA and were in vitro shown to have a transient, fluoxetine sensitive 3H-5-HT uptake. Unilateral denervation of the snout was shown to decrease specific 5-HTT binding in thalamus suggesting that particular pathways may be vulnerable during critical periods. The wide expression of 5-HTT and VMAT mRNAs in the developing embryo suggests potential new roles for monoamines transporters in establishing the wiring of the different sensory pathways as well as maintaining an appropriate microenvironment for migrating and differentiating neural crest cells. Our findings provide a guide for future studies on the role of monoamines during development.