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Erschienen in: Brain Structure and Function 1/2018

16.08.2017 | Original Article

Loss of Kirrel family members alters glomerular structure and synapse numbers in the accessory olfactory bulb

verfasst von: Alexandra C. Brignall, Reesha Raja, Alina Phen, Janet E. A. Prince, Emilie Dumontier, Jean-François Cloutier

Erschienen in: Brain Structure and Function | Ausgabe 1/2018

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Abstract

The accessory olfactory system controls social and sexual behaviours in mice, both of which are critical for their survival. Vomeronasal sensory neuron (VSN) axons form synapses with mitral cell dendrites in glomeruli of the accessory olfactory bulb (AOB). Axons of VSNs expressing the same vomeronasal receptor (VR) converge into multiple glomeruli within spatially conserved regions of the AOB. Here, we have examined the role of the cell adhesion molecule Kirrel2 in the formation of glomeruli within the AOB. We find that Kirrel2 expression is dispensable for early axonal guidance events, such as fasciculation of the vomeronasal tract and segregation of apical and basal VSN axons into the anterior and posterior regions of the AOB, but is necessary for glomeruli formation. Specific ablation of Kirrel2 expression in VSN axons results in the disorganization of the glomerular layer of the posterior AOB and in the formation of fewer and larger glomeruli. Furthermore, simultaneous ablation of Kirrel2 and Kirrel3 expression leads to a loss of morphologically identifiable glomeruli in the AOB, reduced excitatory synapse numbers, and larger presynaptic terminals. Taken together, our results demonstrate that Kirrel2 and Kirrel3 are essential for the formation of glomeruli and suggest they contribute to synaptogenesis in the AOB.
Literatur
Zurück zum Zitat Belluscio L, Koentges G, Axel R, Dulac C (1999) A map of pheromone receptor activation in the mammalian brain. Cell 97:209–220 CrossRefPubMed Belluscio L, Koentges G, Axel R, Dulac C (1999) A map of pheromone receptor activation in the mammalian brain. Cell 97:209–220 CrossRefPubMed
Zurück zum Zitat Boschat C, Pélofi C, Randin O, Roppolo D, Lüscher C, Broillet MC, Rodriguez I (2002) Pheromone detection mediated by a V1r vomeronasal receptor. Nat Neurosci 5:1261–1262 CrossRefPubMed Boschat C, Pélofi C, Randin O, Roppolo D, Lüscher C, Broillet MC, Rodriguez I (2002) Pheromone detection mediated by a V1r vomeronasal receptor. Nat Neurosci 5:1261–1262 CrossRefPubMed
Zurück zum Zitat Brignall AC, Cloutier J-F (2015) Neural map formation and sensory coding in the vomeronasal system. Cell Mol Life Sci 72:4697–4709 CrossRefPubMed Brignall AC, Cloutier J-F (2015) Neural map formation and sensory coding in the vomeronasal system. Cell Mol Life Sci 72:4697–4709 CrossRefPubMed
Zurück zum Zitat Chamero P, Katsoulidou V, Hendrix P, Bufe B, Roberts R, Matsunami H, Abramowitz J, Birnbaumer L, Zufall F, Leinders-Zufall T (2011) G protein Gαo is essential for vomeronasal function and aggressive behavior in mice. Proc Natl Acad Sci USA 108:12898–12903 CrossRefPubMedPubMedCentral Chamero P, Katsoulidou V, Hendrix P, Bufe B, Roberts R, Matsunami H, Abramowitz J, Birnbaumer L, Zufall F, Leinders-Zufall T (2011) G protein Gαo is essential for vomeronasal function and aggressive behavior in mice. Proc Natl Acad Sci USA 108:12898–12903 CrossRefPubMedPubMedCentral
Zurück zum Zitat Cho JH, Prince JE, Cutforth T, Cloutier JF (2011) The pattern of glomerular map formation defines responsiveness to aversive odorants in mice. J Neurosci 31:7920–7926 CrossRefPubMed Cho JH, Prince JE, Cutforth T, Cloutier JF (2011) The pattern of glomerular map formation defines responsiveness to aversive odorants in mice. J Neurosci 31:7920–7926 CrossRefPubMed
Zurück zum Zitat Cho JH, Kam JW, Cloutier JF (2012) Slits and Robo-2 regulate the coalescence of subsets of olfactory sensory neuron axons within the ventral region of the olfactory bulb. Dev Biol 371:269–279 CrossRefPubMed Cho JH, Kam JW, Cloutier JF (2012) Slits and Robo-2 regulate the coalescence of subsets of olfactory sensory neuron axons within the ventral region of the olfactory bulb. Dev Biol 371:269–279 CrossRefPubMed
Zurück zum Zitat Cloutier JF, Giger RJ, Koentges G, Dulac C, Kolodkin AL, Ginty DD (2002) Neuropilin-2 mediates axonal fasciculation, zonal segregation, but not axonal convergence, of primary accessory olfactory neurons. Neuron 33:877–892 CrossRefPubMed Cloutier JF, Giger RJ, Koentges G, Dulac C, Kolodkin AL, Ginty DD (2002) Neuropilin-2 mediates axonal fasciculation, zonal segregation, but not axonal convergence, of primary accessory olfactory neurons. Neuron 33:877–892 CrossRefPubMed
Zurück zum Zitat Cloutier JF, Sahay A, Chang EC, Tessier-Lavigne M, Dulac C, Kolodkin AL, Ginty DD (2004) Differential requirements for semaphorin 3F and Slit-1 in axonal targeting, fasciculation, and segregation of olfactory sensory neuron projections. J Neurosci 24:9087–9096 CrossRefPubMed Cloutier JF, Sahay A, Chang EC, Tessier-Lavigne M, Dulac C, Kolodkin AL, Ginty DD (2004) Differential requirements for semaphorin 3F and Slit-1 in axonal targeting, fasciculation, and segregation of olfactory sensory neuron projections. J Neurosci 24:9087–9096 CrossRefPubMed
Zurück zum Zitat Del Punta K, Puche A, Adams NC, Rodriguez I, Mombaerts P (2002) A divergent pattern of sensory axonal projections is rendered convergent by second-order neurons in the accessory olfactory bulb. Neuron 35:1057–1066 CrossRefPubMed Del Punta K, Puche A, Adams NC, Rodriguez I, Mombaerts P (2002) A divergent pattern of sensory axonal projections is rendered convergent by second-order neurons in the accessory olfactory bulb. Neuron 35:1057–1066 CrossRefPubMed
Zurück zum Zitat Donoviel DB, Freed DD, Vogel H, Potter DG, Hawkins E, Barrish JP, Mathur BN, Turner CA, Geske R, Montgomery CA, Starbuck M, Brandt M, Gupta A, Ramirez-Solis R, Zambrowicz BP, Powell DR (2001) Protreinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN. Mol Cell Biol 21:4829–4836 CrossRefPubMedPubMedCentral Donoviel DB, Freed DD, Vogel H, Potter DG, Hawkins E, Barrish JP, Mathur BN, Turner CA, Geske R, Montgomery CA, Starbuck M, Brandt M, Gupta A, Ramirez-Solis R, Zambrowicz BP, Powell DR (2001) Protreinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN. Mol Cell Biol 21:4829–4836 CrossRefPubMedPubMedCentral
Zurück zum Zitat Dulac C, Axel R (1995) A novel family of genes encoding putative pheromone receptors in mammals. Cell 83:195–206 CrossRefPubMed Dulac C, Axel R (1995) A novel family of genes encoding putative pheromone receptors in mammals. Cell 83:195–206 CrossRefPubMed
Zurück zum Zitat Dulac C, Wagner S (2006) Genetic analysis of brain circuits underlying pheromone signaling. Annu Rev Genet 40:449–467 CrossRefPubMed Dulac C, Wagner S (2006) Genetic analysis of brain circuits underlying pheromone signaling. Annu Rev Genet 40:449–467 CrossRefPubMed
Zurück zum Zitat Eggan K, Baldwin K, Tackett M, Osborne J, Gogos J, Chess A, Axel R, Jaenisch R (2004) Mice cloned from olfactory sensory neurons. Nature 428:44–49 CrossRefPubMed Eggan K, Baldwin K, Tackett M, Osborne J, Gogos J, Chess A, Axel R, Jaenisch R (2004) Mice cloned from olfactory sensory neurons. Nature 428:44–49 CrossRefPubMed
Zurück zum Zitat Haga S, Hattori T, Sato T, Sato K, Matsuda S, Kobayakawa R, Sakano H, Yoshihara Y, Kikusui T, Touhara K (2010) The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor. Nature 466:118–122 CrossRefPubMed Haga S, Hattori T, Sato T, Sato K, Matsuda S, Kobayakawa R, Sakano H, Yoshihara Y, Kikusui T, Touhara K (2010) The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor. Nature 466:118–122 CrossRefPubMed
Zurück zum Zitat Hammen GF, Turaga D, Holy TE, Meeks JP (2014) Functional organization of glomerular maps in the mouse accessory olfactory bulb. Nat Neurosci 17:953–961 CrossRefPubMedPubMedCentral Hammen GF, Turaga D, Holy TE, Meeks JP (2014) Functional organization of glomerular maps in the mouse accessory olfactory bulb. Nat Neurosci 17:953–961 CrossRefPubMedPubMedCentral
Zurück zum Zitat Hasen NS, Gammie SC (2009) Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity. Genes Brain Behav 8:639–649 CrossRefPubMedPubMedCentral Hasen NS, Gammie SC (2009) Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity. Genes Brain Behav 8:639–649 CrossRefPubMedPubMedCentral
Zurück zum Zitat Herrada G, Dulac C (1997) A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 90:763–773 CrossRefPubMed Herrada G, Dulac C (1997) A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 90:763–773 CrossRefPubMed
Zurück zum Zitat Jia C, Halpern M (1996) Subclasses of vomeronasal receptor neurons: differential expression of G proteins (Gi alpha2) and G(o alpha) and segregated projections to the accessory olfactory bulb. Brain Res 719:117–128 CrossRefPubMed Jia C, Halpern M (1996) Subclasses of vomeronasal receptor neurons: differential expression of G proteins (Gi alpha2) and G(o alpha) and segregated projections to the accessory olfactory bulb. Brain Res 719:117–128 CrossRefPubMed
Zurück zum Zitat Juhila J, Lassila M, Roozendaal R, Lehtonen E, Messing M, Langer B, Kerjaschki D, Verbeek JS, Holthofer H (2010) Inducible nephrin transgene expression in podocytes rescues nephrin-deficient mice from perinatal death. Am J Pathol 176:51–63 CrossRefPubMedPubMedCentral Juhila J, Lassila M, Roozendaal R, Lehtonen E, Messing M, Langer B, Kerjaschki D, Verbeek JS, Holthofer H (2010) Inducible nephrin transgene expression in podocytes rescues nephrin-deficient mice from perinatal death. Am J Pathol 176:51–63 CrossRefPubMedPubMedCentral
Zurück zum Zitat Knoll B, Zarbalis K, Wurst W, Drescher U (2001) A role for the EphA family in the topographic targeting of vomeronasal axons. Development 128:895–906 PubMed Knoll B, Zarbalis K, Wurst W, Drescher U (2001) A role for the EphA family in the topographic targeting of vomeronasal axons. Development 128:895–906 PubMed
Zurück zum Zitat Knoll B, Schmidt H, Andrews W, Guthrie S, Pini A, Sundaresan V, Drescher U (2003) On the topographic targeting of basal vomeronasal axons through Slit-mediated chemorepulsion. Development 130:5073–5082 CrossRefPubMed Knoll B, Schmidt H, Andrews W, Guthrie S, Pini A, Sundaresan V, Drescher U (2003) On the topographic targeting of basal vomeronasal axons through Slit-mediated chemorepulsion. Development 130:5073–5082 CrossRefPubMed
Zurück zum Zitat Li M, Armelloni S, Ikehata M, Corbelli A, Pesaresi M, Calvaresi N, Giardino L, Mattinzoli D, Nisticò F, Andreoni S, Puliti A, Ravazzolo R, Forloni G, Messa P, Rastaldi MP (2011) Nephrin expression in adult rodent nervous system and its interaction with glutamate receptors. J Pathol 225:118–128 CrossRefPubMed Li M, Armelloni S, Ikehata M, Corbelli A, Pesaresi M, Calvaresi N, Giardino L, Mattinzoli D, Nisticò F, Andreoni S, Puliti A, Ravazzolo R, Forloni G, Messa P, Rastaldi MP (2011) Nephrin expression in adult rodent nervous system and its interaction with glutamate receptors. J Pathol 225:118–128 CrossRefPubMed
Zurück zum Zitat Martin EA, Muralidhar S, Wang Z, Cervantes DC, Basu R, Taylor MR, Hunter J, Cutforth T, Wilke SA, Ghosh A, Williams ME (2015) The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus. Elife 4:e09395. doi: 10.​7554/​eLife.​09395 CrossRefPubMedPubMedCentral Martin EA, Muralidhar S, Wang Z, Cervantes DC, Basu R, Taylor MR, Hunter J, Cutforth T, Wilke SA, Ghosh A, Williams ME (2015) The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus. Elife 4:e09395. doi: 10.​7554/​eLife.​09395 CrossRefPubMedPubMedCentral
Zurück zum Zitat Martini S, Silvotti L, Shirazi A, Ryba NJ, Tirindelli R (2001) Co-expression of putative pheromone receptors in the sensory neurons of the vomeronasal organ. J Neurosci 21:843–848 PubMed Martini S, Silvotti L, Shirazi A, Ryba NJ, Tirindelli R (2001) Co-expression of putative pheromone receptors in the sensory neurons of the vomeronasal organ. J Neurosci 21:843–848 PubMed
Zurück zum Zitat Matsunami H, Buck LB (1997) A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90:775–784 CrossRefPubMed Matsunami H, Buck LB (1997) A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90:775–784 CrossRefPubMed
Zurück zum Zitat Morikawa Y, Komori T, Hisaoka T, Ueno H, Kitamura T, Senba E (2007) Expression of mKirre in the developing sensory pathways: its close apposition to nephrin-expressing cells. Neurosci 150:880–886 CrossRef Morikawa Y, Komori T, Hisaoka T, Ueno H, Kitamura T, Senba E (2007) Expression of mKirre in the developing sensory pathways: its close apposition to nephrin-expressing cells. Neurosci 150:880–886 CrossRef
Zurück zum Zitat Pantages E, Dulac C (2000) A novel family of candidate pheromone receptors in mammals. Neuron 28:835–845 CrossRefPubMed Pantages E, Dulac C (2000) A novel family of candidate pheromone receptors in mammals. Neuron 28:835–845 CrossRefPubMed
Zurück zum Zitat Papes F, Logan DW, Stowers L (2010) The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141:692–703 CrossRefPubMedPubMedCentral Papes F, Logan DW, Stowers L (2010) The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141:692–703 CrossRefPubMedPubMedCentral
Zurück zum Zitat Pavenstadt H, Kriz W, Kretzler M (2003) Cell biology of the glomerular pedocyte. Physiol Rev 83:253–307 CrossRefPubMed Pavenstadt H, Kriz W, Kretzler M (2003) Cell biology of the glomerular pedocyte. Physiol Rev 83:253–307 CrossRefPubMed
Zurück zum Zitat Prince JE, Cho JH, Dumontier E, Andrews W, Cutforth T, Tessier-Lavigne M, Parnavelas J, Cloutier JF (2009) Robo-2 controls the segregation of a portion of basal vomeronasal sensory neuron axons to the posterior region of the accessory olfactory bulb. J Neurosci 29:14211–14222 CrossRefPubMedPubMedCentral Prince JE, Cho JH, Dumontier E, Andrews W, Cutforth T, Tessier-Lavigne M, Parnavelas J, Cloutier JF (2009) Robo-2 controls the segregation of a portion of basal vomeronasal sensory neuron axons to the posterior region of the accessory olfactory bulb. J Neurosci 29:14211–14222 CrossRefPubMedPubMedCentral
Zurück zum Zitat Prince JEA, Brignall AK, Cutforth T, Shen K, Cloutier J-F (2013) Kirrel-3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression. Development 140:2398–2408 CrossRefPubMedPubMedCentral Prince JEA, Brignall AK, Cutforth T, Shen K, Cloutier J-F (2013) Kirrel-3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression. Development 140:2398–2408 CrossRefPubMedPubMedCentral
Zurück zum Zitat Putaala H, Soininen R, Kilpeläinen P, Wartiovaara J, Tryggvason K (2001) The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death. Hum Mol Genet 10:1–8 CrossRefPubMed Putaala H, Soininen R, Kilpeläinen P, Wartiovaara J, Tryggvason K (2001) The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death. Hum Mol Genet 10:1–8 CrossRefPubMed
Zurück zum Zitat Rodriguez I, Feinstein P, Mombaerts P (1999) Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system. Cell 97:199–208 CrossRefPubMed Rodriguez I, Feinstein P, Mombaerts P (1999) Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system. Cell 97:199–208 CrossRefPubMed
Zurück zum Zitat Rodriguez I, Del Punta K, Rothman A, Ishii T, Mombaerts P (2002) Multiple new and isolated families within the mouse superfamily of V1r vomeronasal receptors. Nat Neurosci 5:134–140 CrossRefPubMed Rodriguez I, Del Punta K, Rothman A, Ishii T, Mombaerts P (2002) Multiple new and isolated families within the mouse superfamily of V1r vomeronasal receptors. Nat Neurosci 5:134–140 CrossRefPubMed
Zurück zum Zitat Ryba NJ, Tirindelli R (1997) A new multigene family of putative pheromone receptors. Neuron 19:371–379 CrossRefPubMed Ryba NJ, Tirindelli R (1997) A new multigene family of putative pheromone receptors. Neuron 19:371–379 CrossRefPubMed
Zurück zum Zitat Serizawa S, Miyamichi K, Takeuchi H, Yamagishi Y, Suzuki M, Sakano H (2006) A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting. Cell 127:1057–1069 CrossRefPubMed Serizawa S, Miyamichi K, Takeuchi H, Yamagishi Y, Suzuki M, Sakano H (2006) A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting. Cell 127:1057–1069 CrossRefPubMed
Zurück zum Zitat Shen K, Bargmann CI (2003) The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans. Cell 112:619–630 CrossRefPubMed Shen K, Bargmann CI (2003) The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans. Cell 112:619–630 CrossRefPubMed
Zurück zum Zitat Shen K, Fetter RD, Bargmann CI (2004) Synaptic specificity is generated by the synaptic guidepost protein SYG-2 and its receptor, SYG-1. Cell 116:869–881 CrossRefPubMed Shen K, Fetter RD, Bargmann CI (2004) Synaptic specificity is generated by the synaptic guidepost protein SYG-2 and its receptor, SYG-1. Cell 116:869–881 CrossRefPubMed
Zurück zum Zitat Walz A, Rodriguez I, Mombaerts P (2002) Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice. J Neurosci 22:4025–4035 PubMed Walz A, Rodriguez I, Mombaerts P (2002) Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice. J Neurosci 22:4025–4035 PubMed
Zurück zum Zitat Walz A, Feinstein P, Khan M, Mombaerts P (2007) Axonal wiring of guanylate cyclase-D-expressing olfactory neurons is dependent on neuropilin 2 and semaphorin 3F. Development 134:4063–4072 CrossRefPubMed Walz A, Feinstein P, Khan M, Mombaerts P (2007) Axonal wiring of guanylate cyclase-D-expressing olfactory neurons is dependent on neuropilin 2 and semaphorin 3F. Development 134:4063–4072 CrossRefPubMed
Zurück zum Zitat Zufall F, Leinders-Zufall T (2007) Mammalian pheromone sensing. Curr Opin Neurobiol 17:483–489 CrossRefPubMed Zufall F, Leinders-Zufall T (2007) Mammalian pheromone sensing. Curr Opin Neurobiol 17:483–489 CrossRefPubMed
Metadaten
Titel
Loss of Kirrel family members alters glomerular structure and synapse numbers in the accessory olfactory bulb
verfasst von
Alexandra C. Brignall
Reesha Raja
Alina Phen
Janet E. A. Prince
Emilie Dumontier
Jean-François Cloutier
Publikationsdatum
16.08.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 1/2018
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-017-1485-0