miR-103/107 regulates left-right asymmetry in zebrafish by modulating Kupffer's vesicle development and ciliogenesis
| Autor: | David Hassel, Lonny Juergensen, Thomas Draebing, Melanie Philipp, Hugo A. Katus, Monika Haeussler, Jana Heigwer, Jens H. Westhoff, Martin D. Burkhalter, Juliane Kutzner |
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| Rok vydání: | 2020 |
| Předmět: |
Embryo
Nonmammalian Heart malformation Biophysics Morphogenesis Biology Biochemistry Cell Line Mesoderm Ciliogenesis medicine Animals Humans Cilia Molecular Biology Zebrafish Body Patterning Cilium Lateral plate mesoderm Gene Expression Regulation Developmental Heart Cell Biology biology.organism_classification Cell biology medicine.anatomical_structure Endoderm NODAL |
| Zdroj: | Biochemical and biophysical research communications. 527(2) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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