Modulations of FOXL2 on Cartilage and Skeletal Development in Mice

Xue Jianli

Abstract：Objective Haploinsufficiency of the Foxl2 transcription factor in humans causes Blepharophimosis/Pto-sis/Epicanthus Inversus syndrome(BPES),characterized by eyelid anomalies and premature ovarian failure.Mice lac-king Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis.Our experiment aims to explore the influence of lacking Foxl2 in postnatal growth and embryonic bone and cartilage formation in mice.Methods Foxl2-/- male mice at different stages of development have been characterized and compared to wild type.Body length and weight were measured and growth curves were created.Skeletons were stained with alcian blue and/or aliza-rin red.Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-Foxl2 an-tibodies followed by confocal microscopy.Analysis of the GH/IGF1 pathway was done evaluating the expression of sev-eral hypothalamic-pituitary-bone axis markers by RT-qPCR.Results Compared to wild-type,Foxl2 null mice are smal-ler and show skeletal abnormalities and defects in cartilage and bone mineralization,with down-regulation of the GH/IGF1 axis.Conclusion Our results support Foxl2 as a master transcription factor in a spectrum of developmental processes,including growth,cartilage and bone formation.