Notch/Her12 signalling modulates, motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer

Notch/Her12 信号调节斑马鱼左右组织者 Foxj1a 下游的运动/不动纤毛比率

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作者:Barbara Tavares #, Raquel Jacinto #, Pedro Sampaio, Sara Pestana, Andreia Pinto, Andreia Vaz, Mónica Roxo-Rosa, Rui Gardner, Telma Lopes, Britta Schilling, Ian Henry, Leonor Saúde, Susana Santos Lopes

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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