Portal, CélineRompolas, PanteleimosLwigale, PeterIomini, Carlo2021-10-062021-10-062019Portal, Céline, Rompolas, Panteleimos, Lwigale, Peter, et al.. "Primary cilia deficiency in neural crest cells models anterior segment dysgenesis in mouse." <i>eLife,</i> 8, (2019) eLife Sciences Publications, Ltd: https://doi.org/10.7554/eLife.52423.https://hdl.handle.net/1911/111481Defects affecting tissues of the anterior segment (AS) of the eye lead to a group of highly debilitating disorders called Anterior Segment Dysgenesis (ASD). Despite the identification of some causative genes, the pathogenesis of ASD remains unclear. Interestingly, several ciliopathies display conditions of the AS. Using conditional targeting of Ift88 with Wnt1-Cre, we show that primary cilia of neural crest cells (NCC), precursors of most AS structures, are indispensable for normal AS development and their ablation leads to ASD conditions including abnormal corneal dimensions, defective iridocorneal angle, reduced anterior chamber volume and corneal neovascularization. Mechanistically, NCC cilia ablation abolishes hedgehog (Hh) signaling in the periocular mesenchyme (POM) canonically activated by choroid-secreted Indian Hh, reduces proliferation of POM cells surrounding the retinal pigment epithelium and decreases the expression of Foxc1 and Pitx2, two transcription factors identified as major ASD causative genes. Thus, we uncovered a signaling axis linking cilia and ASD.engThis article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are creditedJournal articleelife-52423-v2https://doi.org/10.7554/eLife.52423