{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:32:32Z","timestamp":1788877952213,"version":"build-2803163510"},"reference-count":56,"publisher":"The Company of Biologists","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,1]]},"abstract":"<jats:p>The accessory olfactory system controls social and sexual interactions in mice that are crucial for survival. Vomeronasal sensory neurons (VSNs) form synapses with dendrites of second order neurons in glomeruli of the accessory olfactory bulb (AOB). Axons of VSNs expressing the same vomeronasal receptor coalesce into multiple glomeruli within spatially conserved regions of the AOB. Here we examine the role of the Kirrel family of transmembrane proteins in the coalescence of VSN axons within the AOB. We find that Kirrel2 and Kirrel3 are differentially expressed in subpopulations of VSNs and that their expression is regulated by activity. Although Kirrel3 expression is not required for early axonal guidance events, such as fasciculation of the vomeronasal tract and segregation of apical and basal VSN axons in the AOB, it is necessary for proper coalescence of axons into glomeruli. Ablation of Kirrel3 expression results in disorganization of the glomerular layer of the posterior AOB and formation of fewer, larger glomeruli. Furthermore, Kirrel3\u2212\/\u2212 mice display a loss of male-male aggression in a resident-intruder assay. Taken together, our results indicate that differential expression of Kirrels on vomeronasal axons generates a molecular code that dictates their proper coalescence into glomeruli within the AOB.<\/jats:p>","DOI":"10.1242\/dev.087262","type":"journal-article","created":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T08:14:21Z","timestamp":1367482461000},"page":"2398-2408","source":"Crossref","is-referenced-by-count":68,"title":["Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression"],"prefix":"10.1242","volume":"140","author":[{"given":"Janet E. A.","family":"Prince","sequence":"first","affiliation":[{"name":"Montreal Neurological Institute, Centre for Neuronal Survival, 3801 University, Montr\u00e9al, Qu\u00e9bec, H3A 2B4, Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University, Montr\u00e9al, Qu\u00e9bec, H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra C.","family":"Brignall","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, Centre for Neuronal Survival, 3801 University, Montr\u00e9al, Qu\u00e9bec, H3A 2B4, Canada"},{"name":"Department of Anatomy and Cell Biology, McGill University, Montr\u00e9al, Qu\u00e9bec, H3A 2B2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Cutforth","sequence":"additional","affiliation":[{"name":"Office of Research, University of California, Irvine, CA 92697-3175USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305-5020, USA"},{"name":"Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Cloutier","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, Centre for Neuronal Survival, 3801 University, Montr\u00e9al, Qu\u00e9bec, H3A 2B4, Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University, Montr\u00e9al, Qu\u00e9bec, H3A 2B4, Canada"},{"name":"Department of Anatomy and Cell Biology, McGill University, Montr\u00e9al, Qu\u00e9bec, H3A 2B2, Canada"},{"name":"Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042606460872400_R1","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.ydbio.2010.06.013","article-title":"Preferential adhesion maintains separation of ommatidia in the Drosophila eye","volume":"344","author":"Bao","year":"2010","journal-title":"Dev. Biol."},{"key":"2021042606460872400_R2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0031-9384(82)90097-X","article-title":"Olfactory and vomeronasal mediation of ultrasonic vocalizations in male mice","volume":"28","author":"Bean","year":"1982","journal-title":"Physiol. Behav."},{"key":"2021042606460872400_R3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0092-8674(00)80731-X","article-title":"A map of pheromone receptor activation in the mammalian brain","volume":"97","author":"Belluscio","year":"1999","journal-title":"Cell"},{"key":"2021042606460872400_R4","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nn978","article-title":"Pheromone detection mediated by a V1r vomeronasal receptor","volume":"5","author":"Boschat","year":"2002","journal-title":"Nat. Neurosci."},{"key":"2021042606460872400_R5","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev.ne.19.030196.002505","article-title":"Information coding in the vertebrate olfactory system","volume":"19","author":"Buck","year":"1996","journal-title":"Annu. Rev. Neurosci."},{"key":"2021042606460872400_R6","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1101\/gad.13.12.1524","article-title":"Targeting genes for self-excision in the germ line","volume":"13","author":"Bunting","year":"1999","journal-title":"Genes Dev."},{"key":"2021042606460872400_R7","doi-asserted-by":"crossref","first-page":"12898","DOI":"10.1073\/pnas.1107770108","article-title":"G protein G(\u03b1)o is essential for vomeronasal function and aggressive behavior in mice","volume":"108","author":"Chamero","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606460872400_R8","doi-asserted-by":"crossref","first-page":"9094","DOI":"10.1523\/JNEUROSCI.2217-07.2007","article-title":"Requirement for Slit-1 and Robo-2 in zonal segregation of olfactory sensory neuron axons in the main olfactory bulb","volume":"27","author":"Cho","year":"2007","journal-title":"J. Neurosci."},{"key":"2021042606460872400_R9","doi-asserted-by":"crossref","first-page":"7920","DOI":"10.1523\/JNEUROSCI.2460-10.2011","article-title":"The pattern of glomerular map formation defines responsiveness to aversive odorants in mice","volume":"31","author":"Cho","year":"2011","journal-title":"J. Neurosci."},{"key":"2021042606460872400_R10","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S0896-6273(02)00635-9","article-title":"Neuropilin-2 mediates axonal fasciculation, zonal segregation, but not axonal convergence, of primary accessory olfactory neurons","volume":"33","author":"Cloutier","year":"2002","journal-title":"Neuron"},{"key":"2021042606460872400_R11","doi-asserted-by":"crossref","first-page":"9087","DOI":"10.1523\/JNEUROSCI.2786-04.2004","article-title":"Differential requirements for semaphorin 3F and Slit-1 in axonal targeting, fasciculation, and segregation of olfactory sensory neuron projections","volume":"24","author":"Cloutier","year":"2004","journal-title":"J. Neurosci."},{"key":"2021042606460872400_R12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3758\/BF03328867","article-title":"Olfactory control of aggressive and sexual behavior in the mouse","volume":"27","author":"Connor","year":"1972","journal-title":"Psychon. Sci."},{"key":"2021042606460872400_R13","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S0896-6273(02)00904-2","article-title":"A divergent pattern of sensory axonal projections is rendered convergent by second-order neurons in the accessory olfactory bulb","volume":"35","author":"Del Punta","year":"2002","journal-title":"Neuron"},{"key":"2021042606460872400_R14","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0092-8674(95)90161-2","article-title":"A novel family of genes encoding putative pheromone receptors in mammals","volume":"83","author":"Dulac","year":"1995","journal-title":"Cell"},{"key":"2021042606460872400_R15","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1146\/annurev.genet.39.073003.093937","article-title":"Genetic analysis of brain circuits underlying pheromone signaling","volume":"40","author":"Dulac","year":"2006","journal-title":"Annu. Rev. Genet."},{"key":"2021042606460872400_R16","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.neuron.2009.09.027","article-title":"DSCAM and DSCAML1 function in self-avoidance in multiple cell types in the developing mouse retina","volume":"64","author":"Fuerst","year":"2009","journal-title":"Neuron"},{"key":"2021042606460872400_R17","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/cne.21064","article-title":"Neuronal expression and interaction with the synaptic protein CASK suggest a role for Neph1 and Neph2 in synaptogenesis","volume":"498","author":"Gerke","year":"2006","journal-title":"J. Comp. Neurol."},{"key":"2021042606460872400_R18","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature09142","article-title":"The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor","volume":"466","author":"Haga","year":"2010","journal-title":"Nature"},{"key":"2021042606460872400_R19","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1601-183X.2009.00511.x","article-title":"Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity","volume":"8","author":"Hasen","year":"2009","journal-title":"Genes Brain Behav."},{"key":"2021042606460872400_R20","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0092-8674(00)80536-X","article-title":"A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution","volume":"90","author":"Herrada","year":"1997","journal-title":"Cell"},{"key":"2021042606460872400_R21","doi-asserted-by":"crossref","first-page":"7907","DOI":"10.1523\/JNEUROSCI.2399-11.2012","article-title":"Activity regulates functional connectivity from the vomeronasal organ to the accessory olfactory bulb","volume":"32","author":"Hovis","year":"2012","journal-title":"J. Neurosci."},{"key":"2021042606460872400_R22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cne.21396","article-title":"Chemotopic odorant coding in a mammalian olfactory system","volume":"503","author":"Johnson","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"2021042606460872400_R23","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.neuron.2008.01.023","article-title":"BIG-2 mediates olfactory axon convergence to target glomeruli","volume":"57","author":"Kaneko-Goto","year":"2008","journal-title":"Neuron"},{"key":"2021042606460872400_R24","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.1242\/dev.00726","article-title":"On the topographic targeting of basal vomeronasal axons through Slit-mediated chemorepulsion","volume":"130","author":"Kn\u00f6ll","year":"2003","journal-title":"Development"},{"key":"2021042606460872400_R25","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/nn.2452","article-title":"Structural requirements for the activation of vomeronasal sensory neurons by MHC peptides","volume":"12","author":"Leinders-Zufall","year":"2009","journal-title":"Nat. Neurosci."},{"key":"2021042606460872400_R26","doi-asserted-by":"crossref","first-page":"6376","DOI":"10.1073\/pnas.082127599","article-title":"Altered sexual and social behaviors in trp2 mutant mice","volume":"99","author":"Leypold","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606460872400_R27","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.neuron.2007.10.014","article-title":"Development of continuous and discrete neural maps","volume":"56","author":"Luo","year":"2007","journal-title":"Neuron"},{"key":"2021042606460872400_R28","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0092-8674(00)80581-4","article-title":"Combinatorial receptor codes for odors","volume":"96","author":"Malnic","year":"1999","journal-title":"Cell"},{"key":"2021042606460872400_R29","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1523\/JNEUROSCI.21-03-00843.2001","article-title":"Co-expression of putative pheromone receptors in the sensory neurons of the vomeronasal organ","volume":"21","author":"Martini","year":"2001","journal-title":"J. Neurosci."},{"key":"2021042606460872400_R30","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/0031-9384(86)90300-8","article-title":"Mediation of male mouse urine marking and aggression by the vomeronasal organ","volume":"37","author":"Maruniak","year":"1986","journal-title":"Physiol. Behav."},{"key":"2021042606460872400_R31","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S0092-8674(00)80537-1","article-title":"A multigene family encoding a diverse array of putative pheromone receptors in mammals","volume":"90","author":"Matsunami","year":"1997","journal-title":"Cell"},{"key":"2021042606460872400_R32","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nn.2546","article-title":"Representation and transformation of sensory information in the mouse accessory olfactory system","volume":"13","author":"Meeks","year":"2010","journal-title":"Nat. Neurosci."},{"key":"2021042606460872400_R33","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0092-8674(00)81387-2","article-title":"Visualizing an olfactory sensory map","volume":"87","author":"Mombaerts","year":"1996","journal-title":"Cell"},{"key":"2021042606460872400_R34","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1152\/physrev.00021.2005","article-title":"Maps of odorant molecular features in the mammalian olfactory bulb","volume":"86","author":"Mori","year":"2006","journal-title":"Physiol. Rev."},{"key":"2021042606460872400_R35","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S0896-6273(00)00157-4","article-title":"A novel family of candidate pheromone receptors in mammals","volume":"28","author":"Pantages","year":"2000","journal-title":"Neuron"},{"key":"2021042606460872400_R36","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.cell.2010.03.037","article-title":"The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs","volume":"141","author":"Papes","year":"2010","journal-title":"Cell"},{"key":"2021042606460872400_R37","doi-asserted-by":"crossref","first-page":"14211","DOI":"10.1523\/JNEUROSCI.3948-09.2009","article-title":"Robo-2 controls the segregation of a portion of basal vomeronasal sensory neuron axons to the posterior region of the accessory olfactory bulb","volume":"29","author":"Prince","year":"2009","journal-title":"J. Neurosci."},{"key":"2021042606460872400_R38","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/0092-8674(94)90015-9","article-title":"Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb","volume":"79","author":"Ressler","year":"1994","journal-title":"Cell"},{"key":"2021042606460872400_R39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0092-8674(00)80730-8","article-title":"Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system","volume":"97","author":"Rodriguez","year":"1999","journal-title":"Cell"},{"key":"2021042606460872400_R40","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/nn795","article-title":"Multiple new and isolated families within the mouse superfamily of V1r vomeronasal receptors","volume":"5","author":"Rodriguez","year":"2002","journal-title":"Nat. Neurosci."},{"key":"2021042606460872400_R41","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0896-6273(00)80946-0","article-title":"A new multigene family of putative pheromone receptors","volume":"19","author":"Ryba","year":"1997","journal-title":"Neuron"},{"key":"2021042606460872400_R42","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0896-6273(95)90032-2","article-title":"Restricted expression of the irreC-rst protein is required for normal axonal projections of columnar visual neurons","volume":"15","author":"Schneider","year":"1995","journal-title":"Neuron"},{"key":"2021042606460872400_R43","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1126\/science.1089122","article-title":"Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse","volume":"302","author":"Serizawa","year":"2003","journal-title":"Science"},{"key":"2021042606460872400_R44","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.cell.2006.10.031","article-title":"A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting","volume":"127","author":"Serizawa","year":"2006","journal-title":"Cell"},{"key":"2021042606460872400_R45","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0092-8674(03)00113-2","article-title":"The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans","volume":"112","author":"Shen","year":"2003","journal-title":"Cell"},{"key":"2021042606460872400_R46","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S0092-8674(04)00251-X","article-title":"Synaptic specificity is generated by the synaptic guidepost protein SYG-2 and its receptor, SYG-1","volume":"116","author":"Shen","year":"2004","journal-title":"Cell"},{"key":"2021042606460872400_R47","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.conb.2010.02.013","article-title":"Olfactory mechanisms of stereotyped behavior: on the scent of specialized circuits","volume":"20","author":"Stowers","year":"2010","journal-title":"Curr. Opin. Neurobiol."},{"key":"2021042606460872400_R48","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1126\/science.1069259","article-title":"Loss of sex discrimination and male-male aggression in mice deficient for TRP2","volume":"295","author":"Stowers","year":"2002","journal-title":"Science"},{"key":"2021042606460872400_R49","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/0092-8674(94)90029-9","article-title":"Topographic organization of sensory projections to the olfactory bulb","volume":"79","author":"Vassar","year":"1994","journal-title":"Cell"},{"key":"2021042606460872400_R50","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s004270050292","article-title":"Irregular chiasm-C-roughest, a member of the immunoglobulin superfamily, affects sense organ spacing on the Drosophila antenna by influencing the positioning of founder cells on the disc ectoderm","volume":"209","author":"Venugopala Reddy","year":"1999","journal-title":"Dev. Genes Evol."},{"key":"2021042606460872400_R51","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00418-011-0903-2","article-title":"Comparative analysis of Neph gene expression in mouse and chicken development","volume":"137","author":"V\u00f6lker","year":"2012","journal-title":"Histochem. Cell Biol."},{"key":"2021042606460872400_R52","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.neuron.2006.04.033","article-title":"A multireceptor genetic approach uncovers an ordered integration of VNO sensory inputs in the accessory olfactory bulb","volume":"50","author":"Wagner","year":"2006","journal-title":"Neuron"},{"key":"2021042606460872400_R53","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1523\/JNEUROSCI.22-10-04025.2002","article-title":"Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice","volume":"22","author":"Walz","year":"2002","journal-title":"J. Neurosci."},{"key":"2021042606460872400_R54","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1242\/dev.008722","article-title":"Axonal wiring of guanylate cyclase-D-expressing olfactory neurons is dependent on neuropilin 2 and semaphorin 3F","volume":"134","author":"Walz","year":"2007","journal-title":"Development"},{"key":"2021042606460872400_R55","doi-asserted-by":"crossref","first-page":"7375","DOI":"10.1523\/JNEUROSCI.1967-06.2006","article-title":"Pheromone detection in male mice depends on signaling through the type 3 adenylyl cyclase in the main olfactory epithelium","volume":"26","author":"Wang","year":"2006","journal-title":"J. Neurosci."},{"key":"2021042606460872400_R56","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.conb.2007.07.012","article-title":"Mammalian pheromone sensing","volume":"17","author":"Zufall","year":"2007","journal-title":"Curr. Opin. Neurobiol."}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/140\/11\/2398\/1565588\/2398_dev087262.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/140\/11\/2398\/1565588\/2398_dev087262.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T09:09:42Z","timestamp":1619428182000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/140\/11\/2398\/45732\/Kirrel3-is-required-for-the-coalescence-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,1]]},"references-count":56,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2013,6,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.087262","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2013,6,1]]}}}