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Furthermore, a SNP in an enhancer region near VGL元 in humans was recently linked to reduced body mass index (BMI), body-fat and plasma leptin levels 19.
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It is known that fat metabolism is related to age at puberty in mice 18, and interestingly, Vgll3 has been linked to inhibiting adipocyte differentiation in mouse 7.
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Further, oocytes can stimulate proliferation of granulosa cells in mice by inhibiting the Hippo pathway and increasing the activity of Yap1, while activation of the Hippo pathway promotes granulosa cell differentiation during ovulation 17. The pathway has also been linked to ovarian function in human 14 and to regulating granulosa cell proliferation in the ovary of mice 15 and chicken 16. In fact, the pathway can control testicular and ovarian proliferation in Drosophila 11, and recent studies have suggested that the Drosophila orthologs Vg (Vgll) and Sd (Tead) together with Tgi (Vgll4) function as default repressors in gonadal escort cells, while Yki (Yap) antagonizes this repression by competing for binding with Sd 12, 13. Since the Hippo pathway is a regulator of organ development, we hypothesize that it is involved in pubertal development and growth of the gonads. The Hippo pathway consists of several proteins that act in a signalling cascade, which negatively regulates the activity of their main target, the cofactors Yap/Taz, ultimately affecting the ability to interact with the partner transcription factor (e.g. Both Vgll3 and Tead are part of the Hippo signalling pathway, which controls organ size by regulating cell proliferation, differentiation and migration during development of organs 8, 9, 10. Although the roles of the Vestigial-like protein 3 (Vgll3) in vertebrates remain unclear, this cofactor of the Tead family of transcription factors 3 has been implicated in various processes such as onset of puberty 4, 5, autoimmune diseases 6, cancer 3 and fat metabolism 7. Since then, several vestigial-like genes have been connected to various cellular processes in vertebrates 2. First discovered in Drosophila, the vestigial gene was found to control wing development 1.