Ciliopathies are developmental disorders caused by mutations in components of the primary cilium (a microtubule-based mechanosensor organelle present in many mammalian cells), and are usually characterised by multi-organ abnormalities. Congenital lung malformation (pulmonary hypoplasia) often occurs, and is considered the leading cause of death in Meckel-Gruber syndrome (MKS), a lethal ciliopathy associated with mutations in the transmembrane protein 67 gene, Tmem67. To investigate mechanisms of pulmonary hypoplasia in MKS, Colin A. Johnson's group characterised Tmem67−/− knockout mutant mice and used biochemical methods to further elucidate TMEM67 function. The group found that TMEM67 interacts with Wnt5a and receptor tyrosine kinase-like orphan receptor 2 (ROR2), two components of non-canonical Wnt signalling. Tmem67−/− embryos and pups manifest pulmonary hypoplasia phenotypes and, consistent with other available data, these are mediated by mutations of any component in the Wnt5a-TMEM67-ROR2 axis. Interestingly, pharmacological targeting of downstream effectors of this axis is able to rescue pulmonary abnormalities in cultured lungs from Tmem67−/− mice. These results implicate the dysregulation of the Wnt5a-TMEM67-ROR2 axis in ciliopathies and suggest that its downstream modulation can prevent pulmonary hypoplasia in these diseases. Page 527
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IN THIS ISSUE| 01 June 2015
Elucidating pulmonary hypoplasia in ciliopathies
Online Issn: 1754-8411
Print Issn: 1754-8403
© 2015. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Dis Model Mech (2015) 8 (6): e0602.
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Elucidating pulmonary hypoplasia in ciliopathies. Dis Model Mech 1 June 2015; 8 (6): e0602. doi:
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