CEDOC, Chronic Diseases Research Centre, NOVA Medical School - Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
Laboratório de Histologia e Patologia Comparada, Instituto de Medicina Molecular, Centro Académico de Medicina de Lisboa, Lisboa, Portugal.
Elife. 2017 Sep 6;6:e25165. doi: 10.7554/eLife.25165.
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 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 transcription. We demonstrate that overexpression of either 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 expression pattern and left-right (L-R) axis establishment.
Foxj1a 对于运动纤毛的形成是必需且充分的。通过转录研究和慢扫描双光子活细胞成像技术(能够识别运动和非运动纤毛的数量),我们现在确定了运动纤毛的最终数量取决于 Notch 信号(NS)。我们发现,尽管所有的左右组织者(LRO)细胞都表达 [特定基因],并且这些细胞的纤毛轴突具有动力蛋白臂,但有些纤毛仍然是非运动的。我们确定,这个决定是在发育的早期在 Kupffer's Vesicle(KV)前体中做出的,其判断依据是 [特定基因] 的转录。我们证明,过表达 [特定基因] 或 Notch 细胞内结构域(NICD)都会以牺牲运动纤毛为代价增加非运动纤毛的数量,并导致 KV 前半部分积累大量的非运动纤毛。这会破坏正常的流体流动强度和模式,从而对 [特定基因] 的表达模式和左右(L-R)轴的建立产生影响。