Nguyen Thanh Khoa, Rodriguez John-Michael, Wesselman Hannah M, Wingert Rebecca A
Department of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, Boler-Parseghian Center for Rare and Neglected Diseases, Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, IN 46556, USA.
iScience. 2024 Oct 28;27(12):111271. doi: 10.1016/j.isci.2024.111271. eCollection 2024 Dec 20.
Cilia are hair-like organelles with vital physiological roles, and ciliogenesis defects underlie a range of severe congenital malformations and human diseases. Here, we report that is essential for cilia development across multiple embryonic tissues including the ear, neuromasts and Kupffer's vesicle (KV), which establishes left/right axial pattern. deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), determining that is essential to properly establish several renal lineages. Further, deficiency disrupted renal monociliated cells, MCCs and led to aberrant basal body positioning. We reported that regulates prostaglandin biosynthesis in ciliogenesis and renal fate changes through key factors including and PGE. Our findings reveal essential roles of in tissue cilia development, and identify as a critical regulator of prostaglandin biosynthesis during renal development and ciliogenesis, providing insights relevant for future treatments of ciliopathies.
纤毛是具有重要生理作用的毛发状细胞器，纤毛发生缺陷是一系列严重先天性畸形和人类疾病的基础。在此，我们报告， 对于包括耳朵、神经丘和库普弗囊泡（KV）在内的多个胚胎组织中的纤毛发育至关重要，而库普弗囊泡可建立左右轴向模式。 缺陷的胚胎表现出液体稳态改变和肾脏缺陷，包括多纤毛细胞（MCCs）减少，这表明 对于正确建立几个肾谱系至关重要。此外， 缺陷破坏了肾单纤毛细胞、MCCs，并导致基体定位异常。我们报告称， 通过包括 和前列腺素E（PGE）在内的关键因子调节纤毛发生和肾命运变化中的前列腺素生物合成。我们的研究结果揭示了 在组织纤毛发育中的重要作用，并确定 是肾发育和纤毛发生过程中前列腺素生物合成的关键调节因子，为未来纤毛病的治疗提供了相关见解。
