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Curr Biol. 2015 Mar 2;25(5):556-67. doi: 10.1016/j.cub.2014.12.051. Epub 2015 Feb 5.

Intraciliary calcium oscillations initiate vertebrate left-right asymmetry.

Author information

1
Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
2
Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
3
Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: martina.brueckner@yale.edu.
4
Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: zhaoxia.sun@yale.edu.

Abstract

BACKGROUND:

Bilateral symmetry during vertebrate development is broken at the left-right organizer (LRO) by ciliary motility and the resultant directional flow of extracellular fluid. However, how ciliary motility is perceived and transduced into asymmetrical intracellular signaling at the LRO remains controversial. Previous work has indicated that sensory cilia and polycystin-2 (Pkd2), a cation channel, are required for sensing ciliary motility, yet their function and the molecular mechanism linking both to left-right signaling cascades are unknown.

RESULTS:

Here we report novel intraciliary calcium oscillations (ICOs) at the LRO that connect ciliary sensation of ciliary motility to downstream left-right signaling. Utilizing cilia-targeted genetically encoded calcium indicators in live zebrafish embryos, we show that ICOs depend on Pkd2 and are left-biased at the LRO in response to ciliary motility. Asymmetric ICOs occur with onset of LRO ciliary motility, thus representing the earliest known LR asymmetric molecular signal. Suppression of ICOs using a cilia-targeted calcium sink reveals that they are essential for LR development.

CONCLUSIONS:

These findings demonstrate that intraciliary calcium initiates LR development and identify cilia as a functional ion signaling compartment connecting ciliary motility and flow to molecular LR signaling.

PMID:
25660539
PMCID:
PMC4469357
DOI:
10.1016/j.cub.2014.12.051
[Indexed for MEDLINE]
Free PMC Article
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