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Reiter JF, Skarnes WC.. Tectonic, a novel regulator of the Hedgehog pathway required for both activation and inhibition. Genes Dev 20: 22-27

Department of Molecular and Cell Biology , University of California, Berkeley, Berkeley, California, United States
Genes & Development (Impact Factor: 10.8). 02/2006; 20(1):22-7. DOI: 10.1101/gad.1363606
Source: PubMed

ABSTRACT

We report the identification of a novel protein that participates in Hedgehog-mediated patterning of the neural tube. This protein, named Tectonic, is the founding member of a previously undescribed family of evolutionarily conserved secreted and transmembrane proteins. During neural tube development, mouse Tectonic is required for formation of the most ventral cell types and for full Hedgehog (Hh) pathway activation. Epistasis analyses reveal that Tectonic modulates Hh signal transduction downstream of Smoothened (Smo) and Rab23. Interestingly, characterization of Tectonic Shh and Tectonic Smo double mutants indicates that Tectonic plays an additional role in repressing Hh pathway activity.

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    • "This defect is comparable to that observed upon disruption of other TZ proteins in C. elegans, including the MKS module components MKSR-1 (B9d1), MKSR-2 (B9d2), and MKS-6 (Cc2d2a; Williams et al., 2011), and suggests that the TZ functions to promote the localization of certain membrane-associated proteins to the cilium and to prevent the ciliary entry of others. Because of its roles in controlling ciliary composition, the TZ is essential for ciliary signaling and mammalian development (Reiter and Skarnes, 2006; Weatherbee et al., 2009; Dowdle et al., 2011; Garcia-Gonzalo et al., 2011; Sang et al., 2011; Chih et al., 2012). Similarly, Tmem231 is crucial for mouse development: Tmem231 mutant mice develop phenotypes that are hallmarks of MKS, including cystic kidneys, ductal plate malformations, and hindlimb polydactyly. "
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    • "In addition to the Drosophila homologues, mammalian cells have several novel cytoplasmic regulators of Hh signaling, including Rab23 [76] and tectonic[77]. Rab23 and tectonic are negative regulators downstream of SMO, but their exact mechanism of action remains to be elucidated. Unlike many Rab proteins, Rab23 is localized in the nucleus and cytoplasm[78], suggesting that Rab23 may have other uncharacterized functions apart from membrane trafficking. "
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