Serotonin transporter messenger RNA expression in neural crest-derived structures and sensory pathways of the developing rat embryo

A growing body of evidence suggests that serotonin plays an important role in the early development of both neural and non-neural tissues from vertebr ate and invertebrate species. Serotonin is removed from the extracellular s pace by the cocaine- and antidepressant-sensitive serotonin transporter, th ereby limiting its action on receptors. In situ hybridization histochemistr y was used to delineate serotonin transporter messenger RNA expression duri ng rat embryonic development. Serotonin transporter messenger RNA was widel y expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, serotonin transporter messenger RNA nas detected in neural crest cells, some of which respond to serotonin iii vitro, and n eural crest-derived tissues, such as autonomic ganglia, tooth primordia, ad renal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were serotonin transporter messenger RNA-positive: (i) sensory gangl ionic neurons and (ii) neuroepithelial cells, which serve as targets for th e outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained seroton in transporter messenger RNA by late gestation. The expression of serotonin transporter messenger RNA throughout the sensory pathways from central ner vous system relay stations [Hansson S. R. et al. (1997) Neuroscience 83, 11 85-1201; Lebrand C. ci iii. (1996) Neuron 17, 823-835] to sensory nerves an d target organs as shown in tills study suggests that serotonin may regulat e peripheral synaptogenesis, and thereby influence later processing of sens ory stimuli. If the early detection of serotonin transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein a ctivity, it may permit establishment of a serotonin concentration gradient across epithelia, either from serotonin in the amniotic fluid or from neuro nal enteric serotonin, as a developmental cue. Our results demonstrating se rotonin transporter messenger RNA in the craniofacial and cardiac areas ide ntify this gene product as the transporter most likely responsible for the previously identified accumulation of serotonin in skin and tooth germ [Lau der J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. 8, 265 -276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. e t al. (1988) Development 102, 709-720; Shuey D. L. ct al. (1992) Teratology 46, 367-378; Shuey D. L. ei ui. (1993) Anat. Embryol., Berlin 187, 75-85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. 77, 211-21 5; Yavarone M. S. L et al. (1993) Teratology 47, 573-584] malformations. Serotonin transporter messenger RNA was detected in several neural crest ce ll lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of serotonin transporter messenger RNA in ear ly development supports the hypothesis that serotonin may play a role in ne ural crest cell migration and differentiation [Lauder J. M. (1993) Trends N eurosci. 16,233-240], and that the morphogenetic actions of serotonin may b e regulated by transport. The striking pattern of serotonin transporter mes senger RNA throughout developing sensory pathways suggests that serotonin m ay play a role in establishing patterns of connectivity critical to process ing sensory stimuli. As a target for drugs, such as cocaine, amphetamine de rivatives and antidepressants, expression of serotonin transporter during d evelopment may reflect critical periods of vulnerability for fetal drug exp osure. The widespread distribution of serotonin transporter messenger RNA during o ntogeny suggests a previously unappreciated rule of serotonin in diverse ph ysiological systems during embryonic development. (C) 1998 IBRO. Published by Elsevier Science Ltd.