The microcephaly gene WD40-repeat protein 62 (WDR62) regulates cilia formation, chemo- and photo-sensation in Drosophila melanogaster

B Shohayeb1, L Quinn2, S Millard1 and D Ng1

  1. School of Biomedical Science, University of Queensland, St Lucia, Queensland 4067, Australia
  2. School of Biomedical Science, University of Melbourne, Parkville, Victoria 3010, Australia

Cilia are microtubule-based structures (axonemes) that extend from centrioles (basal bodies), which are also principal components of centrosomes. Cilia project from the cell body and perform critical sensory and signalling functions essential for normal development and tissue homeostasis. Ciliary defects cause a myriad of diseases in humans collectively known as ciliopathies. WD40-Repeat Protein 62 (WDR62) is a centrosome and microtubule-associated signalling protein that is genetically linked to the autosomal recessive condition of primary microcephaly. Interestingly, wdr62 mutations cause CNS malformations, behavioural and learning disorders that phenotypically overlap ciliopathies. The molecular and cellular basis of WDR62 functions in brain formation, and whether this involves regulation of the primary cilium remains undefined. Our current study utilized fly genetics to investigate whether the Drosophila wdr62 ortholog (CG7337) was required for cilia formation and function in sensory neurons that innervate chemo- and mechano-sensory bristles in the legs, wings and antennae. We visualized ciliated sensory neurons using neural specific (Elav Gal4) mCD8-GFP expression and observed increased cilia length in the mechanosensory neurons of campaniform sensilla in the wing vein following CG7337 knockdown. Interestingly, cilia formation was deficient in mechanosensory neurons in femoral chordotonal groups in the legs, as well as in the chemosensory neurons in the antennae. Behavioural assays revealed defects in phototaxis and chemosensory responses of third instar larvae consistent with cilia defects observed in adult flies. Thus, our studies show that wdr62/CG7337 has an essential role in regulating cilia formation, which may have implications for mammalian ciliogenesis.