PT  - JOURNAL ARTICLE
AU  - Dylan J.M. Bergen
AU  - Nicola L. Stevenson
AU  - Roderick E.H. Skinner
AU  - David J. Stephens
AU  - Chrissy L. Hammond
TI  - The Golgi matrix protein giantin is required for normal cilia function in zebrafish
AID  - 10.1101/117507
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 117507
4099  - http://biorxiv.org/content/early/2017/03/16/117507.short
4100  - http://biorxiv.org/content/early/2017/03/16/117507.full
AB  - The Golgi is essential for glycosylation of newly synthesised proteins including almost all cell-surface and extracellular matrix proteoglycans. Giantin, encoded by the golgb1 gene, is a member of the golgin family of proteins that reside within the Golgi stack but its function remains elusive. Loss-of-function of giantin in rats causes osteochondrodysplasia; knockout mice show milder defects, notably a cleft palate. In vitro, giantin has been implicated in Golgi organization, biosynthetic trafficking, and ciliogenesis. Here we show that loss-of-function of giantin in zebrafish, using either morpholino or knockout techniques, causes defects in cilia function. Giantin morphants have fewer cilia in the neural tube and those remaining are longer. Mutants have the same number of cilia in the neural tube but these cilia are also elongated. Scanning electron microscopy shows that loss of giantin results in an accumulation of material at the ciliary tip, consistent with a loss-of-function of retrograde intraflagellar transport. Mutants show milder defects than morphants consistent with adaptation to loss of giantin.Summary statement Loss of giantin following either morpholino injection or genome editing in zebrafish results in defects in ciliogenesis.