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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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
22 April 2020
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| In: |
Biochemical and biophysical research communications
Year: 2020, Volume: 527, Issue: 2, Pages: 432-439 |
| ISSN: | 1090-2104 |
| DOI: | 10.1016/j.bbrc.2020.04.066 |
| Online Access: | 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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| Author Notes: | Jana Heigwer, Juliane Kutzner, Monika Haeussler, Martin D. Burkhalter, Thomas Draebing, Lonny Juergensen, Hugo A. Katus, Melanie Philipp, Jens H. Westhoff, David Hassel |
| Summary: | 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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| Item Description: | Gesehen am 14.08.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1090-2104 |
| DOI: | 10.1016/j.bbrc.2020.04.066 |