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 theempty 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.emx2deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), revealing thatemx2is essential to properly establish several renal lineages as well. Further,emx2deficiency disrupted ciliogenesis on renal monociliated cells and MCCs, and led to aberrant basal body positioning in kidney cells. Interestingly, we discovered thatemx2deficiency was associated with reduced expression of key factors which regulate prostaglandin biosynthesis: the transcriptional regulatorperoxisome proliferator-activated receptor gamma 1 alpha (ppargc1a)and its downstream targetprostaglandin-endoperoxide synthase 1 (ptgs1), which encodes a crucial enzyme for production of the prostanoid ligand prostaglandin E2 (PGE2). Importantly, both ciliogenesis and renal fate changes were rescued whenemx2deficient embryos were provided with PGE2 or transcripts encodingptgs1orppargc1a. Taken together, our findings reveal new essential roles ofemx2in cilia development across several tissues, and identifyemx2as a critical, novel regulator of prostaglandin biosynthesis during renal development and ciliogenesis.