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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Autori principali: Heigwer, Jana (Autore) , Kutzner, Juliane (Autore) , Jürgensen, Lonny (Autore) , Katus, Hugo (Autore) , Westhoff, Jens (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 22 April 2020
In: Biochemical and biophysical research communications
Year: 2020, Volume: 527, Fascicolo: 2, Pages: 432-439
ISSN:1090-2104
DOI:10.1016/j.bbrc.2020.04.066
Accesso online:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbrc.2020.04.066
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0006291X20307920
Testo
Note sull'autore: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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Riassunto: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.
Descrizione del documento:Gesehen am 14.08.2020
Descrizione fisica:Online Resource
ISSN:1090-2104
DOI:10.1016/j.bbrc.2020.04.066