Notch/Her12 signalling modulates motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer
- CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Portugal
- Instituto de Medicina Molecular, Centro Académico de Medicina de Lisboa, Portugal
- Instituto Gulbenkian de Ciencia, Portugal
- Max Planck Institute of Molecular Cell Biology and Genetics, Germany
- Instituto de Medicina Molecular, Portugal
Abstract
Foxj1a is necessary and sufficient to specify motile cilia. Using transcriptional studies and slow-scan two-photon live imaging capable of identifying the number of motile and immotile cilia, we now established that the final number of motile cilia depends on Notch signalling (NS). We found that despite all left-right organizer (LRO) cells express foxj1a and the ciliary axonemes of these cells have dynein arms some cilia remain immotile. We identified that this decision is taken early in development in the Kupffer’s Vesicle (KV) precursors the readout being her12 transcription. We demonstrate that overexpression of either her12 or Notch intracellular domain (NICD) increases the number of immotile cilia at the expense of motile cilia, and leads to an accumulation of immotile cilia at the anterior half of the KV. This disrupts the normal fluid flow intensity and pattern, with consequent impact on dand5 expression pattern and left-right (L-R) axis establishment.
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Author details
Susana Santos Lopes
Funding
Fundação para a Ciência e a Tecnologia (PTDC/BEX-BID/1411/2014)
- Susana Santos Lopes
Fundação para a Ciência e a Tecnologia (FCT-ANR/BEX-BID/0153/2012)
- Sara Pestana
Fundação para a Ciência e a Tecnologia (PTDC/SAU-OBD/103981/2008)
- Andreia Vaz
Fundação para a Ciência e a Tecnologia (PD/BD/52420/2013)
- Raquel Jacinto
Fundação para a Ciência e a Tecnologia (SFRH/BPD/77258/2011)
- Barbara Tavares
Fundação para a Ciência e a Tecnologia (SFRH/BD/111611/2015)
- Pedro Sampaio
Fundação para a Ciência e a Tecnologia (IF/00951/2012)
- Susana Santos Lopes
The funders had no role in study design, data collection and interpretation, or the on the decision to submit the work for publication.
Copyright
© 2017, Tavares et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Notch/Her12 signalling modulates motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer
eLife 6:e25165.
https://doi.org/10.7554/eLife.25165
