Non-essential role for cilia in coordinating precise alignment of lens fibres

0472850 - ÚMG 2017 RIV IE eng J - Journal Article
Sugiyama, Y. - Shelley, E.J. - Yoder, B.K. - Kozmik, Zbyněk - May-Simera, H.L. - Beales, P.L. - Lovicu, F.J. - McAvoy, J.W.
Non-essential role for cilia in coordinating precise alignment of lens fibres.
Mechanisms of Development. Roč. 139, FEB 2016 (2016), s. 10-17. ISSN 0925-4773. E-ISSN 1872-6356
R&D Projects: GA ČR GA15-23675S
Institutional support: RVO:68378050
Keywords : Lens * Primary cilium * ift88 * Bardet-Biedl Syndrome (BBS) * Planar cell polarity (PCP)
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 1.333, year: 2016

The primary cilium, a microtubule-based organelle found in most cells, is a centre for mechano-sensing fluid movement and cellular signalling, notably through the Hedgehog pathway. We recently found that each lens fibre cell has an apically situated primary cilium that is polarised to the side of the cell facing the anterior pole of the lens. The direction of polarity is similar in neighbouring cells so that in the global view, lens fibres exhibit planar cell polarity (PCP) along the equatorial-anterior polar axis. Ciliogenesis has been associated with the establishment of PCP, although the exact relationship between PCP and the role of cilia is still controversial. To test the hypothesis that the primary cilia have a role in coordinating the precise alignment/orientation of the fibre cells, IFT88, a key component of the intraflagellar transport (IFT) complex, was removed specifically from the lens at different developmental stages using several lens-specific Cre-expressing mouse lines (MLR10- and LR-Cre). Irrespective of which Cre-line was adopted, both demonstrated that in IFT88-depleted cells, the ciliary axoneme was absent or substantially shortened, confirming the disruption of primary cilia formation. However no obvious histological defects were detected even when IFT88 was removed from the lens placode as early as E9.5. Specifically, the lens fibres aligned/oriented towards the poles to form the characteristic Y-shaped sutures as normal. Consistent with this, in primary lens epithelial explants prepared from these conditional knockout mouse lenses, the basal bodies still showed polarised localisation at the apical surface of elongating cells upon FGF-induced fibre differentiation. We further investigated the lens phenotype in knockouts of Bardet-Biedl Syndrome (BBS) proteins 4 and 8, the components of the BBSome complex which modulate ciliary function...
Permanent Link: http://hdl.handle.net/11104/0270071