Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system

Abstract

The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.DOI: http://dx.doi.org/10.7554/eLife.13715.001

Spatio-temporal pattern of neuronal differentiation in the Drosophila visual system: A user’s guide to the dynamic morphology of the developing optic lobe

“…R7 and R8 establish their final projections in the medullary m6 and m3 layers in a two-step process: R7/R8 first extend their growth cones to the respective temporary layers; by the mid pupal stage, they reach their final target destination (this work; Ting et al, 2005). The molecular network controlling the proper layer targeting of R7 includes Drosophila N-cadherin, along with the phospho-tyrosine phosphatases PTP69D and Lar; while R8 growth cone extension requires Capricious (Caps), Flamingo (fmi, a transmembrane Cadherin) and the putative receptor, Golden Goal (ggo), as well as Robo-3 and Slit (Kulkarni et al, 2016; Hofmeyer and Treisman, 2009; Nern et al, 2008; Tomasi et al, 2008; Chen and Clandinin, 2008; Ting et al, 2005; Lee et al, 2001). Netrins and its receptor, Frazzled (Fra) have been recently identified as additional players in controlling R8 layer specificity (Timofeev et al, 2012).…”

Wiring visual systems: common and divergent mechanisms and principles

“…Similar to development of lateral retinotopic organization, axons and dendrites that end up in the wrong location may form synapses there. Fly R8s that mistarget to the M6 layer in the medulla form aberrant synapses with Dm8 [58], and ectopic photoreceptors created genetically outside of the visual system synapse in brain regions far from their normal environment [59]. However, synapses in the medulla are not strictly layer-specific [37]; consequently, layer-specific targeting is unlikely to be a sufficient determinant of synaptic specificity.…”

sequoia controls the type I>0 daughter proliferation switch in the developing Drosophila nervous system

“…Seq, Ttk and Ham were all found to be dynamically expressed in the developing SOPs (Moore et al, 2002(Moore et al, , 2004Andrews et al, 2009;Endo et al, 2011). In addition, dynamic Seq protein expression levels govern photoreceptor axon targeting to the optic lobe (Petrovic and Hummel, 2008;Kulkarni et al, 2016).…”