Intriguingly, IFT gene mutations also cause eye, kidney and brain ciliopathies often linked to defects in the transition zone (TZ), a ciliary gate implicated in Hedgehog signalling.Here, we identify a <i>C. elegans</i> temperature-sensitive (<i>ts</i>) IFT-dynein mutant (<i>che-3</i>; human DYNC2H1) and use it to show a role for retrograde IFT in anterograde transport and ciliary maintenance.
All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS).
We further substantiate a proposed digenic diallelic inheritance of ciliopathies by the identification of heterozygous mutations in NEK1 and DYNC2H1 in an additional family.