PMID- 16280633 OWN - NLM STAT- MEDLINE DCOM- 20060224 LR - 20190621 IS - 0378-5866 (Print) IS - 0378-5866 (Linking) VI - 27 IP - 6 DP - 2005 TI - Serotonin transporter function is an early step in left-right patterning in chick and frog embryos. PG - 349-63 AB - The neurotransmitter serotonin has been shown to regulate a number of embryonic patterning events in addition to its crucial role in the nervous system. Here, we examine the role of two serotonin transporters, the plasma membrane serotonin transporter (SERT) and the vesicular monoamine transporter (VMAT), in embryonic left-right asymmetry. Pharmacological or genetic inhibitors of either SERT or VMAT specifically randomized the laterality of the heart and viscera in Xenopus embryos. This effect takes place during cleavage stages, and is upstream of the left-sided gene XNR-1. Targeted microinjection of an SERT-dominant negative construct confirmed the necessity for SERT function in embryonic laterality and revealed that the descendants of the right ventral blastomere are the most dependent upon SERT signaling in left-right patterning. Moreover, the importance of SERT and VMAT in laterality is conserved in chick embryos, being upstream of the early left-sided gene Shh. Endogenous transcripts of SERT and VMAT are expressed from the initiation of the primitive streak in chick and are asymmetrically expressed in Hensen's node. Taken together our data characterize two new right-sided markers in chick gastrulation, identify a novel, early component of the left-right pathway in two vertebrate species, and reveal a new biological role for serotonin transport. CI - Copyright (c) 2005 S. Karger AG, Basel. FAU - Fukumoto, Takahiro AU - Fukumoto T AD - Cytokine Biology Department, The Forsyth Institute, Harvard Medical School, Boston, Mass. 02115, USA. FAU - Blakely, Randy AU - Blakely R FAU - Levin, Michael AU - Levin M LA - eng GR - CO6RR11244/CO/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Switzerland TA - Dev Neurosci JT - Developmental neuroscience JID - 7809375 RN - 0 (Hedgehog Proteins) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 0 (Trans-Activators) RN - 0 (Transforming Growth Factor beta) RN - 0 (Vesicular Monoamine Transport Proteins) RN - 0 (Xenopus Proteins) RN - 0 (nodal1 protein, Xenopus) RN - 333DO1RDJY (Serotonin) SB - IM MH - Animals MH - Body Patterning/*genetics MH - Chick Embryo MH - Chickens MH - Embryo, Nonmammalian/cytology/embryology/metabolism MH - Embryonic Development/*genetics MH - Gastrula/cytology/metabolism MH - Gene Expression Regulation, Developmental/*genetics MH - Hedgehog Proteins MH - Organogenesis/genetics MH - Serotonin/metabolism MH - Serotonin Plasma Membrane Transport Proteins/drug effects/*genetics MH - Trans-Activators/genetics MH - Transcriptional Activation/genetics MH - Transforming Growth Factor beta/genetics MH - Vesicular Monoamine Transport Proteins/antagonists & inhibitors/*genetics MH - Xenopus Proteins MH - Xenopus laevis EDAT- 2005/11/11 09:00 MHDA- 2006/02/25 09:00 CRDT- 2005/11/11 09:00 PHST- 2005/04/06 00:00 [received] PHST- 2005/04/22 00:00 [accepted] PHST- 2005/11/11 09:00 [pubmed] PHST- 2006/02/25 09:00 [medline] PHST- 2005/11/11 09:00 [entrez] AID - 88451 [pii] AID - 10.1159/000088451 [doi] PST - ppublish SO - Dev Neurosci. 2005;27(6):349-63. doi: 10.1159/000088451.