Goggolidou, ParaskeviStevens, Jonathan LAgueci, FrancescoKeynton, JenniferWheway, GabrielleGrimes, Daniel TPatel, Saloni HHilton, HelenMorthorst, Stine KDiPaolo, AntonellaWilliams, Debbie JSanderson, JeremyKhoronenkova, Svetlana VPowles-Glover, NicolaErmakov, AlexanderEsapa, Chris TRomero, RosarioDianov, Grigory LBriscoe, JamesJohnson, Colin APedersen, Lotte BNorris, Dominic P2018-10-232018-10-232014-10-072529494110.1242/dev.107755http://hdl.handle.net/2436/621803© 2014 The Authors. Published by The Company of Biologists. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1242/dev.107755Initially identified in DNA damage repair, ATM-interactor (ATMIN) further functions as a transcriptional regulator of lung morphogenesis. Here we analyse three mouse mutants, Atmin(gpg6/gpg6), Atmin(H210Q/H210Q) and Dynll1(GT/GT), revealing how ATMIN and its transcriptional target dynein light chain LC8-type 1 (DYNLL1) are required for normal lung morphogenesis and ciliogenesis. Expression screening of ciliogenic genes confirmed Dynll1 to be controlled by ATMIN and further revealed moderately altered expression of known intraflagellar transport (IFT) protein-encoding loci in Atmin mutant embryos. Significantly, Dynll1(GT/GT) embryonic cilia exhibited shortening and bulging, highly similar to the characterised retrograde IFT phenotype of Dync2h1. Depletion of ATMIN or DYNLL1 in cultured cells recapitulated the in vivo ciliogenesis phenotypes and expression of DYNLL1 or the related DYNLL2 rescued the effects of loss of ATMIN, demonstrating that ATMIN primarily promotes ciliogenesis by regulating Dynll1 expression. Furthermore, DYNLL1 as well as DYNLL2 localised to cilia in puncta, consistent with IFT particles, and physically interacted with WDR34, a mammalian homologue of the Chlamydomonas cytoplasmic dynein 2 intermediate chain that also localised to the cilium. This study extends the established Atmin-Dynll1 relationship into a developmental and a ciliary context, uncovering a novel series of interactions between DYNLL1, WDR34 and ATMIN. This identifies potential novel components of cytoplasmic dynein 2 and furthermore provides fresh insights into the molecular pathogenesis of human skeletal ciliopathies.enAscizAtminCiliogenesisCiliopathyDynll1MouseCiliaJournal articleDevelopment