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

ABSTRACT 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 the empty spiracles homeobox gene 2 (emx2) transcription factor is essential for cilia development across multiple embryonic tissues including the ear, neuromasts and Kupffer’s vesicle (KV), which establishes left/right axial pattern. emx2 deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), revealing that emx2 is essential to properly establish several renal lineages as well. Further, emx2 deficiency disrupted ciliogenesis on renal monociliated cells and MCCs, and led to aberrant basal body positioning in kidney cells. Interestingly, we discovered that emx2 deficiency was associated with reduced expression of key factors which regulate prostaglandin biosynthesis: the transcriptional regulator peroxisome proliferator-activated receptor gamma 1 alpha ( ppargc1a ) and its downstream target prostaglandin-endoperoxide synthase 1 ( ptgs1 ), which encodes a crucial enzyme for production of the prostanoid ligand prostaglandin E2 (PGE 2 ). Importantly, both ciliogenesis and renal fate changes were rescued when emx2 deficient embryos were provided with PGE 2 or transcripts encoding ptgs1 or ppargc1a . Taken together, our findings reveal new essential roles of emx2 in cilia development across several tissues, and identify emx2 as a critical, novel regulator of prostaglandin biosynthesis during renal development and ciliogenesis.