The transition zone: an essential functional compartment of cilia

Cilia are microtubule-based, hair-like organelles that occur on the apical surface of most mammalian cells in G0/G1 of the cell cycle [1], with the exception of bone marrow-derived cells [2]. Defects in cilia structure or function are the cause of a suite of congenital conditions known as ciliopathies, which now include polycystic kidney disease, nephronophthisis, Senior-L？ken syndrome, Bardet-Biedl syndrome (BBS), Joubert syndrome (JBTS) and Meckel-Gruber syndrome (MKS). Most of these conditions vary in the severity of the clinical phenotype, and display extensive allelism [3] and pleiotropy [3-7].There are three general types of cilia, differentiated on the basis of their microtubule structure (Figure？ 1). Cilia with the canonical “9？+？2”microtubule pattern are motile: Motile cilia occur on epithelial cells in the lungs, in the olfactory bulb, in the inner ear as a kinocilium, and in the reproductive tracts of both sexes. Motile cilia in the respiratory tract perform “whip”-like movements to mediate fluid flow [8], although olfactory cilia, despite their 9？+？2 microtubule pattern, are thought to be immotile [9] and kinocilia are moved by deflection [10]. During embryonic development nodal cilia play a crucial role in left-right patterning. They are located at the embryonic node, and although they have a “9？+？0” microtubule pattern they mediate a leftward flow at the node in a “whirlpool”-like manner due to the retention of dynein arms between microtubules. The leftward flow is thought to transport morphogens that are essential for the first step of symmetry breaking in the developmental of the mammalian body plan [2]. The third type of cilia is an immotile (“9？+？0”) primary cilium, which is now known to participate in diverse roles in cell signaling, chemosensation, mechanosensation and thermosensation [11].In quiescent cells, cilia are derived from a mother centriole that migrates to the apical surface of the cell and matures into the basal body. The mother centr