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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. Made available in DSpace on 2017-10-24T13:39:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-09-06 publishersversion published

© 2017, Tavares et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited., 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.