Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease

Abstract

Primary cilia project from the surface of most vertebrate cells and are thought to be sensory organelles. Defects in primary cilia lead to cystic kidney disease, although the ciliary mechanisms that promote and maintain normal renal function remain incompletely understood. In this work, we generated a floxed allele of the ciliary assembly gene Ift20. Deleting this gene specifically in kidney collecting duct cells prevents cilia formation and promotes rapid postnatal cystic expansion of the kidney. Dividing collecting duct cells in early stages of cyst formation fail to properly orient their mitotic spindles along the tubule, whereas nondividing cells improperly position their centrosomes. At later stages, cells lacking cilia have increased canonical Wnt signaling and increased rates of proliferation. Thus, IFT20 functions to couple extracellular events to cell proliferation and differentiation.

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

“…Conventional Ift57 and Kif3a/ Kif3b null mutations in mice lead to early embryonic lethality due to left-right axis defects, accompanied by a loss of nodal cilia (14)(15)(16), suggesting that the IFT-B complex is critical for ciliogenesis. Supporting this idea, the deletion of Ift20 in mouse kidney causes a lack of primary cilia and leads to polycystic kidney disease (17). In addition to the traditional role of IFT in cilium assembly, recent studies have found that an IFT-like particle organized by IFT20 is recruited to the immune synapse for T-cell receptor recycling (18,19).…”

“…To characterize the function of IFT20 in facial development, we disrupted Ift20 in a neural crest-specific manner using the wingless-related MMTV integration site 1 (Wnt1)-Cre driver line (17,29) (Fig. S1 A and B; Ift20:Wnt1-Cre or cKO hereafter).…”

Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin‐binding IFT‐B2 complex

“…In the ciliate Tetrahymena thermophila, knockout of IFT172 or depletion of IFT80 leads to strong ciliary assembly defects (Beales et al , 2007; Tsao & Gorovsky, 2008), and mutations or depletions of IFT80, IFT172, IFT57, IFT54 (elipsa), and IFT38 (qilin) disrupt ciliogenesis and lead to cystic kidneys and curled body axis in zebrafish (Sun et al , 2004; Beales et al , 2007; Omori et al , 2008; Lunt et al , 2009). Most importantly, knockout mice for IFT172 (wimple), IFT57 (Hippi), IFT54 (Traf3IP/MIP‐T3), IFT38 (Cluap1), IFT20, and IFT80 display embryonic lethality highlighting their essential roles in ciliogenesis in mammals (Huangfu et al , 2003; Houde et al , 2006; Jonassen et al , 2008; Berbari et al , 2011; Rix et al , 2011; Pasek et al , 2012). How the peripheral IFT‐B components associate with the core to form a functional IFT‐B complex is currently unknown.…”

Cils et kystes rénaux

“…La question du lien de cette orientation dans le rein reste actuellement controversé. Même si IFT88 est directement impliquée dans ce processus, les résultats diffèrent selon les IFT étudiées [17,18]. Le rôle du cil dans la régula-tion des voies de polarité planaire pourrait passer par le contrôle de la maturation et de la position du centrosome dans l'établissement du fuseau mitotique [47].…”