PUBLICATION
miR-103/107 regulates left-right asymmetry in zebrafish by modulating Kupffer's vesicle development and ciliogenesis
- Authors
- Heigwer, J., Kutzner, J., Haeussler, M., Burkhalter, M.D., Draebing, T., Juergensen, L., Katus, H.A., Philipp, M., Westhoff, J.H., Hassel, D.
- ID
- ZDB-PUB-200427-1
- Date
- 2020
- Source
- Biochemical and Biophysical Research Communications 527(2): 432-439 (Journal)
- Registered Authors
- Hassel, David, Philipp, Melanie
- Keywords
- Cilia, Kupffer’s vesicle, Left-right patterning, Zebrafish, miRNA
- MeSH Terms
-
- Animals
- Body Patterning
- Cell Line
- Cilia/genetics
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental*
- Heart/embryology
- Humans
- Mesoderm/embryology
- Mesoderm/metabolism
- Zebrafish/embryology
- Zebrafish/genetics*
- PubMed
- 32334837 Full text @ Biochem. Biophys. Res. Commun.
Citation
Heigwer, J., Kutzner, J., Haeussler, M., Burkhalter, M.D., Draebing, T., Juergensen, L., Katus, H.A., Philipp, M., Westhoff, J.H., Hassel, D. (2020) miR-103/107 regulates left-right asymmetry in zebrafish by modulating Kupffer's vesicle development and ciliogenesis. Biochemical and Biophysical Research Communications. 527(2):432-439.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping