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Serotonin transporter function is an early step in left-right patterning in chick and frog embryos
Takahiro Fukumoto1, Randy Blakely, Michael Levin
1Cytokine Biology Department, The Forsyth Institute, Harvard Medical School, Boston, Mass. 02115, USA.
Developmental Neuroscience
|November 11, 2005
Summary
Serotonin transporters, SERT and VMAT, are crucial for establishing embryonic left-right asymmetry in vertebrates. Disrupting these transporters randomizes organ laterality by affecting early patterning events.
Area of Science:
- Developmental Biology
- Neuroscience
- Genetics
Background:
- Serotonin regulates embryonic patterning beyond its known role in the nervous system.
- Serotonin transporters, including SERT and VMAT, are key in neurotransmission.
Purpose of the Study:
- To investigate the role of SERT and VMAT in embryonic left-right asymmetry.
- To identify the specific developmental stages and molecular pathways influenced by serotonin transport in laterality.
Main Methods:
- Pharmacological and genetic inhibition of SERT and VMAT in Xenopus embryos.
- Microinjection of SERT-dominant negative constructs.
- Analysis of gene expression (XNR-1, Shh) and asymmetric markers in chick embryos.
Main Results:
- Inhibiting SERT or VMAT randomized heart and visceral laterality in Xenopus embryos.
- The effects were observed during cleavage stages and were upstream of XNR-1.
- SERT function was essential for left-right patterning, particularly in right ventral blastomere descendants.
- Similar roles for SERT and VMAT were found in chick embryos, upstream of Shh.
- SERT and VMAT were asymmetrically expressed in chick Hensen's node.
Conclusions:
- SERT and VMAT are novel, early components of the vertebrate left-right asymmetry pathway.
- Serotonin transport plays a previously unrecognized role in embryonic laterality.
- SERT and VMAT serve as new right-sided markers during chick gastrulation.