, 2005). Whether cilia orient in migrating neurons or glia, or otherwise contribute to the guidance of neural cells, is unexplored. Shh is a this website chemoattractant for migrating neurons and axons (Angot et al., 2008, Bourikas et al., 2005 and Charron et al., 2003). This activity of Shh requires the putative Hh coreceptor Boc (Okada et al., 2006) and does not appear to utilize the canonical Shh pathway, instead activating Src family kinases to regulate growth cone turning (Yam et al., 2009). Despite these unusual features, Shh chemoattractant signaling is Smo dependant (Charron et al., 2003 and Yam et al.,

2009), suggesting a link with the cilium. PDGF-AA directs migration of oligodendrocyte precursor cells (Dubois-Dalcq and Murray, 2000, Kessaris et al., 2006, Kiernan and Ffrench-Constant, 1993 and Woodruff et al., 2001), which could be mediated by primary cilia. Favoring this possibility, oligodendrocytes have primary cilia (A. Peters, personal KPT-330 research buy communication; Cenacchi et al., 1996), and the neuroepithelial cells that generate oligodendrocyte precursors are presumed to be ciliated, given that they respond to Shh (Richardson et al., 1997). Based on current knowledge, the primary cilium is unlikely to provide motive force to a migrating cell

but could potentially sense and amplify a distant guidance signal. The relationship between the primary cilium and Wnt signal transduction is an important problem that, despite considerable study, is unresolved. Canonical, β-catenin-dependent Wnt signaling regulates cell fate and proliferation in the nervous system (Angers and Moon, 2009). The planar cell polarity (PCP) Wnt pathway orients sheets of cells, for example, regulating the convergent extension aminophylline cell movements that lead to neural tube closure. The PCP pathway is increasingly implicated in neuronal migration and axon guidance, in particular in the orderly development of large axon tracts (Tissir and Goffinet, 2010). This last

observation is intriguing because diffusion tensor imaging in Joubert Syndrome patients reveals that both the corticospinal tract and superior cerebellar peduncle make major mistakes in their trajectories (Poretti et al., 2007). Reports on Wnt signaling and cilia diverge from the model of Shh signaling by indicating that primary cilia suppress, rather than mediate, the canonical Wnt pathway. Mice deficient in Kif3a or Ift88 have shown upregulated signaling ( Corbit et al., 2008). Similarly, reduction of certain BBS proteins (named for their association with Bardet-Biedl Syndrome, BBS, Table 2) stabilizes β-catenin in zebrafish and mammalian cells, leading to upregulated expression of canonical Wnt pathway target genes ( Gerdes et al., 2007).