Journal article

Atypical cadherin FAT4 orchestrates lymphatic endothelial cell polarity in response to flow

Kelly L Betterman, Drew L Sutton, Genevieve A Secker, Jan Kazenwadel, Anna Oszmiana, Lillian Lim, Naoyuki Miura, Lydia Sorokin, Benjamin M Hogan, Mark L Kahn, Helen McNeill, Natasha L Harvey



The atypical cadherin FAT4 has established roles in the regulation of planar cell polarity and Hippo pathway signaling that are cell context dependent. The recent identification of FAT4 mutations in Hennekam syndrome, features of which include lymphedema, lymphangiectasia, and mental retardation, uncovered an important role for FAT4 in the lymphatic vasculature. Hennekam syndrome is also caused by mutations in collagen and calcium binding EGF domains 1 (CCBE1) and ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3), encoding a matrix protein and protease, respectively, that regulate activity of the key prolymphangiogenic VEGF-C/VEGFR3 signaling axis by facilitating the proteol..

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University of Melbourne Researchers


Awarded by NHMRC

Awarded by Australian Research Council (ARC)

Awarded by ARC Future Fellowship

Funding Acknowledgements

We thank Chris Brown and staff at the SA Pathology Animal Facility and UniSA Core Animal Facility for animal husbandry. This study used the services of the Australian Phenomics Network Histopathology and Organ Pathology Service (University of Melbourne, Parkville, Australia) and the SAHMRI Histology Slide Scanning Service (Adelaide, Australia). Confocal microscopy and flow cytometry were performed at the Detmold Imaging and Flow Cytometry Facility (UniSA and SA Pathology, Adelaide, Australia). This work was supported by grants from the NHMRC (APP1061365 and APP1146352, to NLH), the Australian Research Council (ARC) (DP150103110, to BMH and NLH), and the Hospital Research Foundation (to NLH). NLH was supported by an ARC Future Fellowship (FT130101254).