@article{4f2b0f39c2204545a91ae12137bf2f3e,
title = "Notch/Her12 signalling modulates, motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer",
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{\textquoteright}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.",
author = "Barbara Tavares and Raquel Jacinto and Pedro Sampaio and Sara Pestana and Andreia Pinto and Andreia Vaz and M{\'o}nica Roxo-Rosa and Rui Gardner and Telma Lopes and Britta Schilling and Ian Henry and Leonor Sa{\'u}de and Lopes, {Susana Santos}",
note = "Funding Information: The authors wish to thank Julian Lewis for the DeltaD antibody, Carl-Philipp Heisenberg for the gift of the transgenic zebrafish line Tg(sox17:GFP), Leonor Sa{\'u}de for the gift of the transgenic zebrafish line Tg(foxj1a:GFP), the homozygous mutant DeltaC/beatm98/tm98, and the her12 in situ probe, and Helena Soares for the Arl13b-GFP construct. We would like to thank Idan Tuval, Domingos Henrique, Rita Teodoro and Ad{\'a}n Guerrero for insightful discussion of the manuscript. We also want to thank the IGC Advanced Image Facility, mainly to Gabriel Martins for advice and the use of Imaris software, and the IGC and CEDOC Fish Facilities. R.J. was supported by the Mechanisms of Disease and Regenerative Medicine (ProRegeM) PhD programme. info:eu-repo/grantAgreement/FCT/3599-PPCDT/112264/PT# info:eu-repo/grantAgreement/FCT/3599-PPCDT/125312/PT# info:eu-repo/grantAgreement/FCT/3599-PPCDT/103981/PT# info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F77258%2F2011/PT# undacao para a Ciencia e a Tecnologia PTDC/BEX-BID/1411/2014 Susana Santos Lopes Fundacao para a Ciencia e a Tecnologia FCT-ANR/BEX-BID/0153/2012 Sara Pestana Fundacao para a Ciencia e a Tecnologia PTDC/SAU-OBD/103981/2008 Andreia Vaz Fundacao para a Ciencia e a Tecnologia PD/BD/52420/2013 Raquel Jacinto Fundacao para a Ciencia e a Tecnologia SFRH/BPD/77258/2011 Barbara Tavares Fundacao para a Ciencia e a Tecnologia SFRH/BD/111611/2015 Pedro Sampaio Fundacao para a Ciencia 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.",
year = "2017",
month = sep,
day = "6",
doi = "10.7554/eLife.25165",
language = "English",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}