Different levels of the Tripartite motif protein, Anomalies in sensory axon patterning (Asap), regulate distinct axonal projections of Drosophila sensory neurons

Abstract

The axonal projection pattern of sensory neurons typically is regulated by environmental signals, but how different sensory afferents can establish distinct projections in the same environment remains largely unknown. Drosophila class IV dendrite arborization (C4da) sensory neurons project subtype-specific axonal branches in the ventral nerve cord, and we show that the Tripartite motif protein, Anomalies in sensory axon patterning (Asap) is a critical determinant of the axonal projection patterns of different C4da neurons. Asap is highly expressed in C4da neurons with both ipsilateral and contralateral axonal projections, but the Asap level is low in neurons that have only ipsilateral projections. Mutations in asap cause a specific loss of contralateral projections, whereas overexpression of Asap induces ectopic contralateral projections in C4da neurons. We also show by biochemical and genetic analysis that Asap regulates Netrin signaling, at least in part by linking the Netrin receptor Frazzled to the downstream effector Pico. In the absence of Asap, the sensory afferent connectivity within the ventral nerve cord is disrupted, resulting in specific larval behavioral deficits. These results indicate that different levels of Asap determine distinct patterns of axonal projections of C4da neurons by modulating Netrin signaling and that the Asap-mediated axonal projection is critical for assembly of a functional sensory circuit.

Trim9Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory

“…Neogenin, which is closely related to DCC, is predicted to interact with TRIM9 (Meyerhardt et al, 1997;Morikawa et al, 2011). Netrin and neogenin are involved in dendritic selfavoidance in Drosophila melanogaster (Smith et al, 2012), which may be consistent with altered dendritic arborization observed in hippocampal neurons following netrin stimulation or Trim9 de- letion.…”

“…Deletion of Trim9 increases hippocampal dendritic and axonal complexity in vitro TRIM9 regulates the branching and guidance of axons of developing murine cortical neurons (Winkle et al, 2014;Menon et al, 2015) and in invertebrates (Hao et al, 2010;Morikawa et al, 2011;Morf et al, 2013). TRIM9 is present in cultured hippocampal neurons, where its expression increases over time in vitro (Fig.…”

“…The interaction between TRIM9 and the netrin receptor DCC is conserved in invertebrate orthologs, where it modulates cellular response to netrin, including axon guidance, branching, and cell migration (Hao et al, 2010;Morikawa et al, 2011;Winkle et al, 2014). Loss of the Trim9 ortholog in Caenorhabditis elegans is associated with a failure in migration of the anchor cell toward an asymmetric netrin source (Morf et al, 2013;Wang et al, 2014).…”

“…In invertebrates, Trim9 orthologs are implicated in netrin-dependent cell migration, axon guidance, and branching (Hao et al, 2010;Morikawa et al, 2011;Morf et al, 2013). In Drosophila, neural activity regulates TRIM9 expression to establish sensory afferent topographic maps (Yang et al, 2014).…”

Adult Drosophila sensory neurons specify dendritic territories independently of dendritic contacts through the Wnt5–Drl signaling pathway

“…For MARCM analysis, v'ada MARCM clones were generated and examined as described previously (Morikawa et al 2011). Females of hsFLP 122 , ppk-GAL4 UAS-mCD8GFP; tub-GAL80 FRT2A/TM6B were mated with males of the following genotypes: (1) trio E4.1 FRT2A/TM6B, (2) UAS-trio; trio E4.1 FRT2A/TM6B, and (3) yw, FRT2A.…”