The RNA-Binding Protein SBR (Dm NXF1) Is Required for the Constitution of Medulla Boundaries in Drosophila Melanogaster Optic Lobes

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The RNA-Binding Protein SBR (Dm NXF1) Is Required for the Constitution of Medulla Boundaries in Drosophila Melanogaster Optic Lobes cells Article The RNA-Binding Protein SBR (Dm NXF1) Is Required for the Constitution of Medulla Boundaries in Drosophila melanogaster Optic Lobes Ludmila Mamon 1, Anna Yakimova 2, Daria Kopytova 3 and Elena Golubkova 1,* 1 Department of Genetics and Biotechnology, Saint-Petersburg State University, Universitetskaya Emb. 7/9, 199034 St. Petersburg, Russia; [email protected] or [email protected] 2 A. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva Str. 4, 249036 Obninsk, Russia; [email protected] 3 Institute of Gene Biology, Russian Academy of Sciences, Vavilov St. 34/5, 119334 Moscow, Russia; [email protected] * Correspondence: [email protected] or [email protected] Abstract: Drosophila melanogaster sbr (small bristles) is an orthologue of the Nxf1 (nuclear export factor 1) genes in different Opisthokonta. The known function of Nxf1 genes is the export of various mRNAs from the nucleus to the cytoplasm. The cytoplasmic localization of the SBR protein indicates that the nuclear export function is not the only function of this gene in Drosophila. RNA-binding protein SBR enriches the nucleus and cytoplasm of specific neurons and glial cells. In sbr12 mutant males, the disturbance of medulla boundaries correlates with the defects of photoreceptor axons pathfinding, axon bundle individualization, and developmental neurodegeneration. RNA-binding protein SBR Citation: Mamon, L.; Yakimova, A.; participates in processes allowing axons to reach and identify their targets. Kopytova, D.; Golubkova, E. The RNA-Binding Protein SBR (Dm Keywords: neurogenesis; optic lobe; Drosophila; NXF; RNA-binding protein NXF1) Is Required for the Constitution of Medulla Boundaries in Drosophila melanogaster Optic Lobes. Cells 2021, 10, 1144. https://doi.org/ 1. Introduction 10.3390/cells10051144 Drosophila melanogaster sbr (small bristles) is an orthologue of the Nxf1 (nuclear export factor 1) genes in different organisms, including human [1–3]. The best known function of Academic Editor: Krzysztof Jagla the Nxf1 genes is the transport of various mRNAs from the nucleus to the cytoplasm [1]. NXF1 is localized in the nucleus or the nuclear envelope according to its function [4]. As Received: 18 April 2021 we have shown previously, D. melanogaster SBR (Dm NXF1) is located not only in the Accepted: 6 May 2021 Published: 10 May 2021 nucleus but also in the cytoplasm of different cells [5–7]. This finding suggests that the SBR protein has specific cytoplasmic functions in addition to its participation in nuclear Drosophila Publisher’s Note: MDPI stays neutral export of mRNAs. In the larval brain, SBR forms granules in the neuron bodies with regard to jurisdictional claims in and neurites [7]. Some granules contain two RNA-binding proteins, SBR and dFMR1 published maps and institutional affil- (drosophila Fragile Mental Retardation 1), which are known components of RNP-granules. iations. Others are marked by either FMR1 or SBR. These observations suggest that SBR has specific localized RNA targets in the cytoplasm [8]. Regulated translation of localized mRNAs is a widespread and essential process during neurogenesis [9]. Neurogenesis in Drosophila is a highly organized process that requires strict reg- ulation of the compartments individualization and the establishment of the correct Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. connections between neurons. Intercellular communications are an important mediator This article is an open access article of axon guidance, proper axon bundle track, and neuron survival [10–12]. Together with distributed under the terms and RNA binding proteins, localized RNAs in complex create a system of rapid and long-term conditions of the Creative Commons production of signal or receptor molecules near cellular membranes of glial cells, neurons Attribution (CC BY) license (https:// and their neurites. This determines intercellular communications and allows for the creativecommons.org/licenses/by/ appropriate boundaries to be established between the compartments in the brain. The 4.0/). optic lobes of the fly brain are a model of neuropil compartmentalization, playing a Cells 2021, 10, 1144. https://doi.org/10.3390/cells10051144 https://www.mdpi.com/journal/cells Cells 2021, 10, x FOR PEER REVIEW 2 of 15 appropriate boundaries to be established between the compartments in the brain. The optic lobes of the fly brain are a model of neuropil compartmentalization, playing a crucial Cells 2021, 10, 1144 role in the development of the nervous system. Each of the optic lobes 2is of divided 15 into four brain compartments (neuropils): lamina, medulla, lobula, and lobula plate [13]. The compound eyes of D. melanogaster consist of single units called ommatidia. Each crucialommatidium role in the contains development eight of phot the nervousoreceptor system. neurons Each of (R1–R8) the optic that lobes project is divided into the optic lobe intoof the four brain brain compartmentsfollowing the (neuropils): neural superposition lamina, medulla, rule lobula, [14,15]. and lobula This plate rule [13 ensures]. that the The compound eyes of D. melanogaster consist of single units called ommatidia. Each axons from the retina cells obtain information from the same point in space projected onto ommatidium contains eight photoreceptor neurons (R1–R8) that project into the optic lobethe same of the braincartridge following of the the lamina neural superpositionor column of rule the [medulla.14,15]. This The rule axons ensures of that the photoreceptor theneurons axons fromR1–R6 the retinaform cellsthe obtainlamina information plexus in from a retinotopic the same point manner, in space su projectedbdividing the lamina ontoneuropil the same into cartridge synaptic of the laminacartridges. or column Each of thecartridge medulla. Thecontains axons of terminals the photore- of the R1–R6 ceptorphotoreceptor neurons R1–R6 neurons form thelocated lamina in plexus the neighbor in a retinotopicing ommatidia manner, subdividing and detect the the same visual lamina neuropil into synaptic cartridges. Each cartridge contains terminals of the R1–R6 photoreceptorpoint of space neurons [16]. locatedThe axons in the of neighboring the R7–R8 ommatidia photoreceptor and detect neurons the same cross visual the lamina and pointterminate of space in [ 16the]. Themedulla axons of(Figure the R7–R8 1) [17,18]. photoreceptor neurons cross the lamina and terminate in the medulla (Figure1)[17,18]. Figure 1. Location of the axon terminals of the R1–R8 photoreceptor neurons in an optic lobe of the imagoFigure brain. 1. Location The R1–R6 of axons the axon terminate terminals in the lamina of the (depicted R1–R8 inph green),otoreceptor and the R8neurons (blue) and in R7an optic lobe of the (violet)imago axons brain. terminate The R1–R6 in the axons medulla termin (from [ate18] in with the changes). lamina (depicted in green), and the R8 (blue) and R7 (violet) axons terminate in the medulla (from [18] with changes). Morphological defects in the optic lobes and ellipsoid body are the dominant features of sbr12 mutant males, characterized by low activity in the negative geotaxis test [19]. We discussMorphological the role of the sbr defects (Dm nxf1) ingene the inoptic establishing lobes and medulla ellipsoid compartment body are boundaries the dominant features inofDrosophila sbr12 mutant melanogaster males,optic characterized lobes. The defects by low of the activity photoreceptor in the axonsnegative pathfinding, geotaxis test [19]. We axondiscuss bundle the individualization,role of the sbr (Dm and nxf1) developmental gene in establishing neurodegeneration medulla are essentialcompartment for boundaries the formation of medulla boundaries in sbr12 mutant males. Non-random cytoplasmic localizationin Drosophila of RNA-binding melanogaster protein optic SBR lobes. suggests The itdefects plays a roleof the in thephotoreceptor processes allowing axons pathfinding, axonsaxon tobundle reach and individualization, identify their targets. and developmental neurodegeneration are essential for the formation of medulla boundaries in sbr12 mutant males. Non-random cytoplasmic 2.localization Materials and of MethodsRNA-binding protein SBR suggests it plays a role in the processes allowing 2.1. Strains and Hybrids axons to reach and identify their targets. The vitally important D. melanogaster gene sbr (Dm nxf1) is located on the X chro- mosome, whereas the orthologous nxf1 genes of vertebrates are located on autosomal chromosomes.2. Materials Sinceand homozygousMethods or hemizygous carriage of the sbr12 allele is lethal, viable 12 12 male2.1. Strains carriers ofandsbr Hybridscan be obtained by crossing sbr /FM6 females with males that carry sbr+ as a part of the Dp(1;Y)y+v+ duplication on the Y chromosome. sbr12/Dp(1;Y)y+v+ malesThe differ vitally from wild important type males notD. onlymelanogaster in the presence gene of thesbr mutant (Dm sbrnxf112 allele,) is theylocated on the X alsochromosome, have two copies whereas of the thesbr orthologousgene. In sbr12 nxf1/Dp(1;Y)y genes+v+ ofmales, vertebrates the extra aresbr +locatedallele on autosomal lieschromosomes. on the Y chromosome. Since homozygous This fact is especially or hemizygous important carriage for genes normallyof the sbr localized12 allele is lethal, viable on the X chromosome. The transcriptional level of X chromosome-linked genes is regu- male carriers of sbr12 can
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