Photoreceptor-Derived Activin Promotes Dendritic Termination and Restricts the Receptive Fields of First-Order Interneurons in Drosophila

Abstract

SUMMARY How CNS neurons form appropriately sized dendritic fields to encounter their presynaptic partners is poorly understood. The Drosophila medulla is organized in layers and columns, and innervated by medulla neurons dendrites and photoreceptor axons. Here we show that three types of medulla projection (Tm) neurons extend their dendrites in stereotyped directions and to distinct layers within a single column for processing retinotopic information. In contrast, the Dm8 amacrine neurons form a wide dendritic field to receive ~16 R7 photoreceptor inputs. R7- and R8-derived Activin/TGF-β selectively restricts the dendritic fields of their respective postsynaptic partners, Dm8 and Tm20, to the size appropriate for their functions. Canonical Activin signaling promotes dendritic termination without affecting dendritic routing direction or layer. Tm20 neurons lacking Activin signaling expanded their dendritic fields and aberrantly synapsed with neighboring photoreceptors. We suggest that afferent-derived Activin regulates the dendritic field size of their postsynaptic partners to ensure appropriate synaptic partnership.

Multiple Redundant Medulla Projection Neurons Mediate Color Vision inDrosophila

“…Thus, we crossed the ort C1a GAL4 DBD flies, to a number of enhancer trap VP16AD lines to generate combinatorial driver lines that specifically drive expression in Tm5a/b, Tm5c and Tm20 neuronal subtypes (Figures 4B–I, Karuppudurai et al, 2014; Ting et al, 2014). However, Tm20-GAL4 UAS-TNTE animals (Ting et al, 2014) (see Methods for genotypes) exhibited normal learning (Figure 5b). Similar results were obtained with Tm20-LexA / LexAop - TNT::HA flies, indicating that the output of Tm20 is not exclusively required for color entrainment.…”

Development of Dendritic Form and Function

“…The signal is transmitted in a circuit-specific manner because R7-specific Activin knockdown or cell ablation affects only Dm8, whereas equivalent experiments targeting R8 affect only Tm20 (Figure 6c). Moreover, increasing the activity of this receptor-ligand system at the R7-Dm8 synapse decreases Dm8 arbor size, suggesting that this system could be tuned to generate a variety of coverage factors (Ting et al 2014). Given that TGFβ superfamily molecules are implicated in dendrite growth in the mammalian nervous system (Osório et al 2013), it will be interesting to see if their mechanism of action and the outcome for receptive field size is similar to what has been described in Drosophila.…”

“…Postsynaptic partners include a medulla projection neuron called Tm20, which makes one-to-one connections with R8, and an interneuron called Dm8, which receives input from ∼16 R7 cells (Figure 6c) (Ting et al 2014). Activin, a TGFβ superfamily ligand secreted by R7 and R8 afferents, regulates each cell's receptive field size.…”

Activin signaling balances proliferation and differentiation of ovarian niche precursors and enables adjustment of niche numbers

“…Babo phosphorylates the R-Smad Smox (Smad on X), which, together with the Smad4 homolog Medea, translocates to the nucleus and represses or activates various target genes (Brummel et al, 1999). Activin has been associated with proliferation, differentiation and morphogenetic events occurring in the nervous system, immune system, muscle and during imaginal disc development (Bai et al, 2013;Brummel et al, 1999;Clark et al, 2011;Ellis et al, 2010;Ng, 2008;Parker et al, 2006;Peterson and O'Connor, 2013;Ting et al, 2014;Yu et al, 2013;Zheng et al, 2003;Zhu et al, 2008). Activin signaling also acts systemically to control metamorphosis by promoting the expression of several ecdysone biosynthetic enzymes (Gibbens et al, 2011).…”