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TIGM on the cover of Nature Cell Biology 11, 1225 - 1232 (2009)

The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development

The planar cell polarity (PCP) signalling pathway is essential for embryonic development because it governs diverse cellular behaviours, and 'core PCP' proteins, such as Dishevelled and Frizzled, have been extensively characterized. By contrast, the 'PCP effector' proteins, such as Intu and Fuz, remain largely unstudied. These proteins are essential for PCP signalling, but they have never been investigated in mammals and their cell biological activities remain entirely unknown. We report here that Fuz mutant mice show neural tube defects, skeletal dysmorphologies and Hedgehog signalling defects stemming from disrupted ciliogenesis. Using bioinformatics and imaging of an in vivo mucociliary epithelium, we established a central role for Fuz in membrane trafficking, showing that Fuz is essential for trafficking of cargo to basal bodies and to the apical tips of cilia. Fuz is also essential for exocytosis in secretory cells. Finally, we identified a Rab-related small GTPase as a Fuz interaction partner that is also essential for ciliogenesis and secretion. These results are significant because they provide new insights into the mechanisms by which developmental regulatory systems such as PCP signalling interface with fundamental cellular systems such as the vesicle trafficking machinery.

TIGM maintains the world's largest C57BL/6N gene trap library, a knockout mouse embryonic stem (ES) cell resource that contains over 350,000 cell lines representing more than 10,000 unique genes. This library contains multiple clones for each gene to ensure the successful creation of knockout mice.

TIGM also has access to a privately held 129/SvEvBrd gene trap library. This gene trap library contains more than 270,000 sequence-tagged embryonic stem cell clones in the 129/SvEvBrd mouse strain representing mutations in over 9,000 genes. The National Institutes of Health has obtained rights to a subset of these lines, allowing TIGM to make them available for distribution to the academic research community on a subsidized basis.

Together, these established resources provide unparalleled coverage of the mouse genome with over 640,000 cell lines representing over 13,000 genes. TIGM provides ES cell clones and knockout mice to the international scientific community.

Publication describing our library and technology can be found here:
Genome Res. 2008 Oct;18(10):1670-9.

The Texas A&M Institute for Genomic Medicine (TIGM) is a part of the Texas A&M University System as a research institute of the Texas A&M Health Science Center. TIGM utilizes advanced technologies to discover breakthroughs in science and medicine and accelerate the pace of medical discoveries. TIGM accomplishes this through internal research and collaborations with other institutions. TIGM also maintains the world's largest library of mouse knockout embryonic stem cells and provides both ES cells and mice to academic and commercial institutions around the world.