Nat. showed that Shh signaling was disrupted. Thus, in the neural tube, the floor plate was not specified posteriorly even as expression of the Shh mediator Gli2 increased. By contrast, the Shh signaling domain name was expanded in the anterior neural tube and anterior limb bud, consistent with reduced Gli3-repressor (Gli3R) function. The latter probably accounted for the preaxial digit duplication exhibited by the mutants. Overall, these findings indicate that centriole localization of Mks1 is required for ciliogenesis of motile and non-motile cilia, but not for centriole assembly. On the basis of these results, we hypothesize a role for the B9 domain name in mother centriole targeting, a possibility that warrants further future investigations. INTRODUCTION Cilia are PF-06751979 highly conserved microtubule-based organelles that project from the cell surface and are built on a basal body template derived from the centrosome. Cilia can be motile or non-motile and are found widely, from unicellular organisms such as to man (Ibanez-Tallon et al., 2003). Cilia assembly is regulated by a conserved mechanism involving transport mediated by intraflagellar transport (IFT) proteins organized in large multiprotein complexes. Cilia serve diverse functions that can entail mediating cell motility and generating fluid flow, or mediating sensory functions such as the detection of light, odorants, protein ligands and other chemicals, as well as mediating mechanosensation for the detection of shear stress, flow and other forces (Eggenschwiler and Anderson, 2007; Gerdes et al., 2009; Satir and Christensen, 2007; Sharma et al., 2008). During embryonic development, motile cilia at the embryonic node generate PF-06751979 directional fluid flow, which, together with non-motile PF-06751979 sensory cilia at IL20RB antibody the node periphery, propagates signals that establish the left-right body axis (Hirokawa et al., 2006; McGrath et al., 2003; Okada et al., 2005). Thus, some of the mutations causing left-right patterning defects have been shown to encode proteins that are required for motile function of the cilium, such as left-right dynein expressed in motile cilia of the embryonic node (Supp et al., 1997), or mutations in IFT proteins required for node ciliogenesis, such as Polaris (IFT88) (Murcia et al., 2000) and THM1 (IFT139) (Tran et al., 2008). Primary cilia also have been shown to have other important functions during embryonic development through their multitude of sensory functions. They mediate the transduction of sonic hedgehog (Shh) signaling by regulating the processing of Gli transcription factors, which are localized in the cilia (Wong and Reiter, 2008). In mammals, Gli2 and Gli3 play essential roles in anterior-posterior patterning of the limb bud, in dorsoventral patterning of the neural tube, and in other developmental processes (Wong and Reiter, 2008). Patched, the Shh receptor, together with Smoothened (Smo) have been shown to regulate proteolytic cleavage of full-length activator Gli3 (Gli3A) into Gli3 repressor (Gli3R) (Haycraft et al., 2005; Hooper and Scott, 2005; McMahon et al., 2003; Rohatgi et al., 2007; Wang et al., 2000). Shh also inhibits the processing and degradation of Gli2, with Gli2 being rapidly degraded in the absence of Shh (Pan et al., 2006). The cilium also plays an important role in planar cell polarity (PCP; also referred to as non-canonical Wnt signaling) (Gerdes and Katsanis, 2008) through proteins localized in the cilia, such as Kif3a (Corbit et al., 2008) and inversin (Invs) (Shiba et al., 2009; Simons et al., 2005). Mutations in IFT88 disrupt PCP-regulated patterning of stereocilia PF-06751979 bundles in hair cells of the cochlea (Jones et al., 2008). It has also been suggested that polycystic kidney disease, often seen in cilia mutants, might arise from disturbance in the balance between.