Emx2 is an essential regulator of ciliated cell development across embryonic tissues

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 <i>empty spiracles homeobox 2 (emx2)</i> is essential for cilia development across multiple embryonic tissues including the ear, neuromasts and Kupffer's vesicle (KV), which establishes left/right axial pattern. <i>emx2</i> deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), determining that <i>emx2</i> is essential to properly establish several renal lineages. Further, <i>emx2</i> deficiency disrupted renal monociliated cells, MCCs and led to aberrant basal body positioning. We reported that <i>emx2</i> regulates prostaglandin biosynthesis in ciliogenesis and renal fate changes through key factors including <i>ppargc1a, ptgs1</i> and PGE₂. Our findings reveal essential roles of <i>emx2</i> in tissue cilia development, and identify <i>emx2</i> as a critical regulator of prostaglandin biosynthesis during renal development and ciliogenesis, providing insights relevant for future treatments of ciliopathies.