The irre Cell Recognition Module (IRM) Protein Kirre Is Required to Form the Reciprocal Synaptic Network of L4 Neurons in theDrosophilaLamina

Abstract

Each neuropil module, or cartridge, in the fly's lamina has a fixed complement of cells. Of five types of monopolar cell interneurons, only L4 has collaterals that invade neighboring cartridges. In the proximal lamina, these collaterals form reciprocal synapses with both the L2 of their own cartridge and the L4 collateral branches from two other neighboring cartridges. During synaptogenesis, L4 collaterals strongly express the cell adhesion protein Kirre, a member of the irre cell recognition module (IRM) group of proteins ( Fischbach et al., 2009 , J Neurogenet, 23, 48-67). The authors show by mutant analysis and gene knockdown techniques that L4 neurons develop their lamina collaterals in the absence of this cell adhesion protein. Using electron microscopy (EM), the authors demonstrate, however, that without Kirre protein these L4 collaterals selectively form fewer synapses. The collaterals of L4 neurons of various genotypes reconstructed from serial-section EM revealed that the number of postsynaptic sites was dramatically reduced in the absence of Kirre, almost eliminating any synaptic input to L4 neurons. A significant reduction of presynaptic sites was also detected in kirre(0) mutants and gene knockdown flies using RNA interference. L4 neuron reciprocal synapses are thus almost eliminated. A presynaptic marker, Brp-short(GFP) confirmed these data using confocal microscopy. This study reveals that removing Kirre protein specifically disrupts the functional L4 synaptic network in the Drosophila lamina.

Establishment and Maintenance of Neural Circuit Architecture

“…This manipulation positioned the dbd axon terminal adjacent to the A08a lateral arbor. In this new subcellular location, dbd formed functional synapses with the A08a lateral arbor, as Nose et al, 1997;Lee et al, 2001;Yamagata et al, 2002;Shen and Bargmann, 2003;Ango et al, 2004;Shen et al, 2004;Prakash et al, 2005;Dean and Dresbach, 2006;Serizawa et al, 2006;Chen and Clandinin, 2008;Kurusu et al, 2008;Yamagata and Sanes, 2008;Woo et al, 2009;DeNardo et al, 2012;Hong et al, 2012;Antinucci et al, 2013;Enneking et al, 2013;Mizumoto and Shen, 2013;Schwabe et al, 2013;Soto et al, 2013;Ashrafi et al, 2014;Duan et al, 2014;Kuwako et al, 2014;Lüthy et al, 2014;Krishnaswamy et al, 2015;Martin et al, 2015;Früh et al, 2016;Mountoufaris et al, 2017;X. Xie et al, 2017;Berns et al, 2018;Ashley et al, 2019;Cheng et al, 2019;Courgeon and Desplan, 2019;Menon et al, 2019;Tai et al, 2019;Vaddadi et al, 2019 Schuster et al, 1996;Dunah et al, 2005;Robbins et al, 2010;Zonta et al, 2011;…”

Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies

“…We conclude that continuous stimulation leads to the selective accumulation of presynaptic transmembrane receptors, including Chaoptin and CadN, specifically in the most proximal part of photoreceptor terminals. Amongst lamina neurons, only L4 specifically forms synapses at the most proximal end of photoreceptor axon terminals (Fischbach and Dittrich, 1989;Luthy et al, 2014;Rivera-Alba et al, 2011;Tadros et al, 2016). L4 neurons function in the detection of progressive motion (Tuthill et al, 2013) and are cholinergic based on the expression of the vesicular acetylcholine transporter and choline acetyltransferase (ChAT) (Davis et al, 2020;Kolodziejczyk et al, 2008).…”

Untangling the wiring of theDrosophilavisual system: developmental principles and molecular strategies

“…In particular, all tetrad and triad synapses containing more than one L4 are absent. A model in which Kirre is required to stabilize synapses containing a pair of L4 neurons fits with this finding (Lüthy et al, 2014).…”