Convergent extension movements and ciliary function are mediated by ofd1 , a zebrafish orthologue of the human oral-facial-digital type 1 syndrome gene
Open Access
- 29 October 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 18 (2), 289-303
- https://doi.org/10.1093/hmg/ddn356
Abstract
In humans, OFD1 is mutated in oral-facial-digital type I syndrome leading to prenatal death in hemizygous males and dysmorphic faces and brain malformations, with polycystic kidneys presenting later in life in heterozygous females. To elucidate the function of Ofd1, we have studied its function during zebrafish embryonic development. In wild-type embryos, ofd1 mRNA is widely expressed and Ofd1-green fluorescent protein (GFP) fusion localizes to the centrosome/basal body. Disrupting Ofd1 using antisense morpholinos (MOs) led to bent body axes, hydrocephalus and oedema. Laterality was randomized in the brain, heart and viscera, likely a consequence of shorter cilia with disrupted axonemes and perturbed intravesicular fluid flow in Kupffer's vesicle. Embryos injected with ofd1 MOs also displayed convergent extension (CE) defects, which were enhanced by loss of Slb/Wnt11 or Tri/Vangl2, two proteins functioning in a non-canonical Wnt/Planar Cell Polarity (PCP) pathway. Pronephric glomerular midline fusion was compromised in vangl2 and ofd1 loss of function embryos and we suggest this anomaly may be a novel CE defect. Thus, Ofd1 is required for ciliary motility and function in zebrafish, supporting data showing that Ofd1 is essential for primary cilia function in mice. In addition, our data show that Ofd1 is important for CE during gastrulation, consistent with data linking primary cilia and non-canonical Wnt/PCP signalling.Keywords
This publication has 80 references indexed in Scilit:
- Mutations inHydinimpair ciliary motility in miceThe Journal of cell biology, 2008
- The mouse homeobox gene Noto regulates node morphogenesis, notochordal ciliogenesis, and left–right patterningProceedings of the National Academy of Sciences of the United States of America, 2007
- Csrp1 regulates dynamic cell movements of the mesendoderm and cardiac mesoderm through interactions with Dishevelled and DiversinProceedings of the National Academy of Sciences of the United States of America, 2007
- Diversin regulates heart formation and gastrulation movements in developmentProceedings of the National Academy of Sciences of the United States of America, 2006
- Defective planar cell polarity in polycystic kidney diseaseNature Genetics, 2005
- Vertebrate Smoothened functions at the primary ciliumNature, 2005
- Van Gogh-like2 (Strabismus) and its role in planar cell polarity and convergent extension in vertebratesTrends in Genetics, 2004
- Hedgehog signalling in the mouse requires intraflagellar transport proteinsNature, 2003
- Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulationNature, 2000
- Stages of embryonic development of the zebrafishDevelopmental Dynamics, 1995