Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 527, Issue 2, Pages 432-439Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.04.066
Keywords
Zebrafish; miRNA; Kupffer's vesicle; Cilia; Left-right patterning
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Funding
- Dietmar Hopp Stiftung
- Tschira Stiftung
- German Centre for Cardiovascular Research
- Heidelberg Biosciences International Graduate School (HBIGS)
- Deutsche Forschungsgemeinschaft (DFG) [HA 52819/4-1]
- Ministry for Science, Research and Arts of BadenWuerttemberg (MWK)
- Deutsche Stiftung fur Herzforschung (DSHF)
- German Federal Ministry of Education and Research (BMBF) [01ZX1409A]
- DFG [PH 144/4-1, PH 144/6-1]
- Boehringer Ingelheim Ulm Initiative (C9)
- International Graduate School in Molecular Medicine at Ulm University
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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. (C) 2020 Elsevier Inc. All rights reserved.
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