Notch signalling regulates left-right asymmetry through ciliary length control
Copyright policy )Notch signalling regulates left-right asymmetry through ciliary length control
The importance of cilia in embryonic development and adult physiology is emphasized by human ciliopathies. Despite its relevance, molecular signalling pathways behind cilia formation are poorly understood. We show that Notch signalling is a key pathway for cilia length control. In deltaD zebrafish mutants, cilia length is reduced in Kupffer's vesicle and can be rescued by the ciliogenic factor foxj1a. Conversely, cilia length increases when Notch signalling is hyperactivated. Short cilia found in deltaD mutants reduce the fluid flow velocity inside Kupffer's vesicle, thus compromising the asymmetric expression of the flow sensor charon. Notch signalling brings together ciliary length control and fluid flow hydrodynamics with transcriptional activation of laterality genes. In addition, our deltaD mutant analysis discloses an uncoupling between gut and heart laterality.
- Instituto Gulbenkian de Ciência Portugal
- Brown University United States
- University of Lisbon Portugal
- Gulbenkian Institute for Molecular Medicine Portugal
- INSTITUTO DE MEDICINA MOLECULAR Portugal
Embryo, Nonmammalian, Receptors, Notch, Gene Expression Regulation, Developmental, Nerve Tissue Proteins, Organ Size, Water-Electrolyte Balance, Zebrafish Proteins, Animals, Genetically Modified, Intestines, Animals, Cilia, Intestinal Mucosa, Zebrafish, Body Patterning, Protein Binding, Signal Transduction
Embryo, Nonmammalian, Receptors, Notch, Gene Expression Regulation, Developmental, Nerve Tissue Proteins, Organ Size, Water-Electrolyte Balance, Zebrafish Proteins, Animals, Genetically Modified, Intestines, Animals, Cilia, Intestinal Mucosa, Zebrafish, Body Patterning, Protein Binding, Signal Transduction
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