Fate Map of Serotonin Transporter‐Expressing Cells in Developing Mouse Thyroid

Abstract

A Cre/loxP-based fate mapping approach was used to follow the regions of the mouse thyroid labeled by the serotonin transporter SERT. Reporter gene expression (lacZ) is activated by Cre expression from the SERT locus in SERT Cre/þ ;ROSA26R compound mouse embryos. Cell labeling, first detected in the thyroid primordium at the E10.5 prenatal stage, was followed until the postnatal day P30. The co-localization of lacZ staining in the same cells that express the transcription factors Nkx2.1 and Pax8 at the E12.5 stage confirms their identity as thyroid cell precursors. SERT immunohistochemistry on thyroid sections of E18.5 embryos showed SERT expression in thyroid follicular cells. Western blotting analysis confirmed the expression of the protein in adult thyroid tissue and cultured FRTL-5 cells. These results describe the fate of SERT-expressing cells during thyroid development, suggesting an active role of SERT in the development and functions of mammalian thyroid. They also highlight the possibility to use the SERT-Cre mouse line as a good Cre driver in early thyroid development. Anat Rec, 294:384-390, 2011. V V C 2011 Wiley-Liss, Inc.Key words: serotonin transporter (SERT); Cre-recombination; immunohistochemistry; thyroid; development Multiple lines of evidence suggest that serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the early development of neural and non-neural tissues of both vertebrate and invertebrate species (Hansson et al., 1999;Herlenius and Lagercrantz, 2001;Gaspar et al., 2003;Vitalis and Parnavelas, 2003;Li, 2006;Dubé and Amireault, 2007). The monoamine is already detected in the fertilized egg and, prior to the time that it assumes its role as a neurotransmitter, 5-HT is involved in the early morphogenesis of the heart, the cranial mesenchyme, the notochord, neural crest derivatives, and the brain (Shuey et al., 1992;Hansson et al., 1999). Both morphogenetic and neurotransmitter activities of 5-HT are strictly regulated by its transporter SERT (gene name: solute carrier SLC6A4), which modulates the 5-HT concentration in the extracellular fluids. During development, SERT is expressed much more broadly than in adults in several non-serotonin neurons of the brain and in neural crest derivatives (Hansson et al., 1999;Narboux-Nême et al., 2008). The developmental expression of SERT and the high affinity uptake of 5-HT serves the purpose of controlling locally the level of 5-HT regulating the state of activation of 5-HT

Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses

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EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU-depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB

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Targeted Metabolomic Analysis of a Mucopolysaccharidosis IIIB Mouse Model Reveals an Imbalance of Branched-Chain Amino Acid and Fatty Acid Metabolism

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