Convergent extension movements and ciliary function are mediated by ofd1 , a zebrafish orthologue of the human oral-facial-digital type 1 syndrome …

MI Ferrante, L Romio, S Castro… - Human molecular …, 2009 - academic.oup.com
MI Ferrante, L Romio, S Castro, JE Collins, DA Goulding, DL Stemple, AS Woolf, SW Wilson
Human molecular genetics, 2009academic.oup.com
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 …
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.
Oxford University Press