Notch signalling regulates left-right asymmetry through ciliary length control

SS Lopes, R Lourenço, L Pacheco, N Moreno… - …, 2010 - journals.biologists.com
SS Lopes, R Lourenço, L Pacheco, N Moreno, J Kreiling, L Saúde
Development, 2010journals.biologists.com
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 …
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.
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