miR-103/107 regulates left-right asymmetry in zebrafish by modulating Kupffer’s vesicle development and ciliogenesis

In zebrafish, cilia movement within the Kupffer’s vesicle (KV) generates a fluid flow responsible for accumulating nodal signals exclusively in the left lateral plate mesoderm, thereby initiating left-right patterning (LRP). Defects in LRP cause devastating congenital disorders including congenital...

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Hauptverfasser: Heigwer, Jana (VerfasserIn) , Kutzner, Juliane (VerfasserIn) , Jürgensen, Lonny (VerfasserIn) , Katus, Hugo (VerfasserIn) , Westhoff, Jens (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 22 April 2020
In: Biochemical and biophysical research communications
Year: 2020, Jahrgang: 527, Heft: 2, Pages: 432-439
ISSN:1090-2104
DOI:10.1016/j.bbrc.2020.04.066
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbrc.2020.04.066
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0006291X20307920
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Verfasserangaben:Jana Heigwer, Juliane Kutzner, Monika Haeussler, Martin D. Burkhalter, Thomas Draebing, Lonny Juergensen, Hugo A. Katus, Melanie Philipp, Jens H. Westhoff, David Hassel

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520 |a In zebrafish, cilia movement within the Kupffer’s vesicle (KV) generates a fluid flow responsible for accumulating nodal signals exclusively in the left lateral plate mesoderm, thereby initiating left-right patterning (LRP). Defects in LRP cause devastating congenital disorders including congenital heart malformations due to organ mis-positioning. We identified the miR-103/107 family to be involved in regulating LRP. Depletion of miR-103/107 in zebrafish embryos resulted in malpositioned and malformed visceral organs and hearts due to disturbed LRP gene expression, indicating early defects in LRP. Additionally, loss of miR-103/107 affected KV morphogenesis and cilia formation without disturbing endoderm development. Human fibroblasts depleted of miR-103a/107 often failed to extend cilia or developed shorter cilia, indicating functional conservation between species. We identified arl6, araf and foxH1 as direct targets of miR-103/107 providing a mechanistic link to cilia development and nodal signal titration. We describe a new microRNA family controlling KV development and hence influencing establishment of internal organ asymmetry. 
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