SUMMARYBranching morphology is a hallmark feature of axons and dendrites and is essential for neuronal connectivity. To understand how this develops, I analyzed the stereotyped pattern of Drosophila mushroom body (MB) neurons, which have single axons branches that extend dorsally and medially. I found that components of the Wnt/Planar Cell Polarity (PCP) pathway control MB axon branching. frizzled mutant animals showed a predominant loss of dorsal branch extension, whereas strabismus (also known as Van Gogh) mutants preferentially lost medial branches. Further results suggest that Frizzled and Strabismus act independently. Nonetheless, branching fates are determined by complex Wnt/PCP interactions, including interactions with Dishevelled and Prickle that function in a context-dependent manner. Branching decisions are MB-autonomous but non-cell-autonomous as mutant and non-mutant neurons regulate these decisions collectively. I found that Wnt/PCP components do not need to be asymmetrically localized to distinct branches to execute branching functions. However, Prickle axonal localization depends on Frizzled and Strabismus.
KEY WORDS: Axon Branching, Planar cell polarity (PCP), DrosophilaWnt/PCP proteins regulate stereotyped axon branch extension in Drosophila Julian Ng*
DEVELOPMENT
166As branch formation might involve cell-polarizing mechanisms, I decided to study components of the Wnt/Planar Cell Polarity (PCP) pathway. The Wnt/PCP pathway represents a major class of regulators that control planar cell polarity (also termed tissue polarity or planar polarity). This has been extensively studied in Drosophila patterning of the adult cuticle in the wing, abdomen and notum, in the Drosophila eye and in sensory hair cells of the inner ear in mice (Klein and Mlodzik, 2005;Jones and Chen, 2007;Wang and Nathans, 2007;Strutt, 2009;Vladar et al., 2009). The Wnt/PCP pathway acts to orient cells along an axis so that all cells exhibit a grouped polarity. These genes can act both cellautonomously (intracellularly) and non-autonomously (intercellularly between neighboring cells).Despite extensive studies, how they function is unclear and several distinct models are proposed, based principally on Drosophila results (Klein and Mlodzik, 2005;Lawrence et al., 2007;Strutt and Strutt, 2009;Vladar et al., 2009). One key finding is that a seven-pass transmembrane protein Frizzled (Fz) is essential (Gubb and Garcia-Bellido, 1982;Vinson and Adler, 1987;Vinson et al., 1989). How Fz regulates tissue polarity is much debated. One model suggests 'core' components of the Wnt/PCP pathway act to localize Fz asymmetrically within cells (Strutt, 2001;Strutt, 2003;Klein and Mlodzik, 2005;Strutt and Strutt, 2009;Vladar et al., 2009). Acting as an anti-Fz factor, the four-pass transmembrane protein Strabismus (Stbm, also known as Van Gogh or Vang) is thought to act intracellularly to restrict Fz localization to the pole opposite of Stbm (Jenny et al., 2003;Amonlirdviman et al., 2005;Klein and Mlodzik, 2005;Vladar et al., 2009). Interestingly, in g...