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.
Lopes
Susana S
SS
Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Lourenço
Raquel
R
Pacheco
Luís
L
Moreno
Nuno
N
Kreiling
Jill
J
Saúde
Leonor
L
D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics*; D002923:Cilia / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009929:Organ Size / Q000235:genetics; D011485:Protein Binding; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000235:genetics / Q000502:physiology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C468126:dld protein, zebrafish