, 1:P75,
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Date: 16 Nov 2012

A novel role for the obesity-associated gene FTO in ciliogenesis and Wnt signalling

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Common intronic variants in hFTO, an oxoglutarate-dependent dioxygenase, were identified in GWAS to cause a predisposition to obesity. Inactivation of Fto in human and mouse models results in reduced viability, postnatal growth retardation, enhanced metabolism and loss of adipose tissue. However, the function of Fto during development and obesity remains unclear. We sought to clarify the function of Fto using zebrafish and cell culture. In zebrafish, we found loss of fto results in a ciliopathy-like phenotype. Morphants display small eyes, curved tails, otolith defects, disorganised melanocytes, situs inversus and renal cysts. Concurrently, cilia were absent in the olfactory bulbs and disorganised in the pronephric ducts (PND) and neural tube. Functional analysis of motile cilia in the PND and Kupffer’s vesicle confirmed a direct ciliary defect. Wnt signalling has been implicated in adipogenesis and therefore we decided to investigate whether Fto may interact at this level. We found th ...