Semaphorin signaling in the development and function of the gonadotropin hormone-releasing hormone system

Frontiers in Endocrinology

Volumn 4, Issue SEP, 2013, Pages

  Messina, Andrea ^a,b   Giacobini, Paolo ^a,b  

^a JEAN PIERRE AUBERT RESEARCH CENTER   (France)

^b UNIV LILLE   (France)

Author keywords

Cell migration; Development; Gonadotropin releasing hormone; Neuronal plasticity; Reproduction

Indexed keywords

EID: 84885980407     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2013.00133     Document Type: Review

References (109)

1. Kolodkin AL, Matthes DJ, Goodman CS. The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell (1993) 75:1389-99. doi:10.1016/0092-8674(93)90625-Z.
2. Semaphorin Nomenclature Committee. Unified nomenclature for the semaphorins/collapsins. Cell (1999) 97:551-2. doi:10.1016/S0092-8674(00)80766-7.
3. Liu H, Juo ZS, Shim AH, Focia PJ, Chen X, Garcia KC, et al. Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1. Cell (2010) 142:749-61. doi:10.1016/j.cell.2010.07.040.
4. Nogi T, Yasui N, Mihara E, Matsunaga Y, Noda M, Yamashita N, et al. Structural basis for semaphorin signalling through the plexin receptor. Nature (2010) 467:1123-7. doi:10.1038/nature09473.
5. Janssen BJ, Robinson RA, Pérez-Brangulí F, Bell CH, Mitchell KJ, Siebold C, et al. Structural basis of semaphorin-plexin signalling. Nature (2010) 467:1118-22.
6. Tamagnone L, Comoglio PM. Signalling by semaphorin receptors:cell guidance and beyond. Trends Cell Biol (2000) 10:377-83. doi:10.1016/S0962-8924(00)01816-X.
7. Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, et al. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell (1999) 99:71-80. doi:10.1016/S0092-8674(00)80063-X.
8. Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y, Kalb RG, et al. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell (1999) 99:59-69. doi:10.1016/S0092-8674(00)80062-8.
9. Kruger RP, Aurandt J, Guan KL. Semaphorins command cells to move. Nat Rev Mol Cell Biol (2005) 6:789-800. doi:10.1038/nrm1740.
10. Zhou Y, Gunput RA, Pasterkamp RJ. Semaphorin signaling:progress made and promises ahead. Trends Biochem Sci (2008) 33:161-70. doi:10.1016/j.tibs.2008.01.006.
11. Neufeld G, Kessler O. The semaphorins:versatile regulators of tumour progression and tumour angiogenesis. Nat Rev Cancer (2008) 8:632-45. doi:10.1038/nrc2404.
12. Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, et al. The semaphorin 4D receptor controls invasive growth by coupling with Met. Nat Cell Biol (2002) 4:720-4. doi:10.1038/ncb843.
13. Conrotto P, Valdembri D, Corso S, Serini G, Tamagnone L, Comoglio PM, et al. Sema4D induces angiogenesis through Met recruitment by Plexin B1. Blood (2005) 105:4321-9. doi:10.1182/blood-2004-07-2885.
14. Giacobini P, Messina A, Morello F, Ferraris N, Corso S, Penachioni J, et al. Semaphorin 4D regulates gonadotropin hormone-releasing hormone-1 neuronal migration through PlexinB1-Met complex. J Cell Biol (2008) 183:555-66. doi:10.1083/jcb.200806160.
15. Swiercz JM, Kuner R, Offermanns S. Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2. J Cell Biol (2004) 165:869-80. doi:10.1083/jcb.200312094.
16. Toyofuku T, Zhang H, Kumanogoh A, Takegahara N, Suto F, Kamei J, et al. Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2. Genes Dev (2004) 18:435-47. doi:10.1101/gad.1167304.
17. Pasterkamp RJ, Peschon JJ, Spriggs MK, Kolodkin AL. Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature (2003) 424:398-405. doi:10.1038/nature01790.
18. Suzuki K, Okuno T, Yamamoto M, Pasterkamp RJ, Takegahara N, Takamatsu H, et al. Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature (2007) 446:680-4. doi:10.1038/nature05652.
19. Casazza A, Fazzari P, Tamagnone L. Semaphorin signals in cell adhesion and cell migration:functional role and molecular mechanisms. Adv Exp Med Biol (2007) 600:90-108. doi:10.1007/978-0-387-70956-7_8.
20. Tran TS, Kolodkin AL, Bharadwaj R. Semaphorin regulation of cellular morphology. Annu Rev Cell Dev Biol (2007) 23:263-92. doi:10.1146/annurev.cellbio.22.010605.093554.
21. Pasterkamp RJ. Getting neural circuits into shape with semaphorins. Nat Rev Neurosci (2012) 13:605-18. doi:10.1038/nrn3302.
22. Perala N, Sariola H, Immonen T. More than nervous:the emerging roles of plexins. Differentiation (2012) 83:77-91. doi:10.1016/j.diff.2011.08.001.
23. Capparuccia L, Tamagnone L. Semaphorin signaling in cancer cells and in cells of the tumor microenvironment-two sides of a coin. J Cell Sci (2009) 122:1723-36. doi:10.1242/jcs.030197.
24. Ch'ng ES, Kumanogoh A. Roles of Sema4D and Plexin-B1 in tumor progression. Mol Cancer (2010) 9:251. doi:10.1186/1476-4598-9-251.
25. Ojeda SR, Skinner MK. Physiology of the gonadotropin-releasing hormone neuronal network. In:Knobil E, Neill JD, editors. Physiology of Reproduction. New York:Raven Press (2006). p. 2061-126.
26. Wray S. From nose to brain:development of gonadotrophin-releasing hormone-1 neurones. J Neuroendocrinol (2010) 22:743-53. doi:10.1111/j.1365-2826.2010.02034.x.
27. Schwanzel-Fukuda M, PfaffDW. Origin of luteinizing hormone-releasing hormone neurons. Nature (1989) 338:161-4. doi:10.1038/338161a0.
28. Wray S, Grant P, Gainer H. Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode. Proc Natl Acad Sci U S A (1989) 86:8132-6. doi:10.1073/pnas.86.20.8132.
29. Gonzalez-Martinez D, Hu Y, Bouloux PM. Ontogeny of GnRH and olfactory neuronal systems in man:novel insights from the investigation of inherited forms of Kallmann's syndrome. Front Neuroendocrinol (2004) 25:108-30. doi:10.1016/j.yfrne.2004.06.001.
30. Marin O, Rubenstein JL. Cell migration in the forebrain. Annu Rev Neurosci (2003) 26:441-83. doi:10.1146/annurev.neuro.26.041002.131058.
31. Wray S. Development of gonadotropin-releasing hormone-1 neurons. Front Neuroendocrinol (2002) 23:292-316. doi:10.1016/S0091-3022(02)00001-8.
32. Schwarting GA, Wierman ME, Tobet SA. Gonadotropin-releasing hormone neuronal migration. Semin Reprod Med (2007) 25:305-12. doi:10.1055/s-2007-984736.
33. Wierman ME, Kiseljak-Vassiliades K, Tobet S. Gonadotropin-releasing hormone (GnRH) neuron migration:initiation, maintenance and cessation as critical steps to ensure normal reproductive function. Front Neuroendocrinol (2011) 32:43-52. doi:10.1016/j.yfrne.2010.07.005.
34. Giger RJ, Wolfer DP, De Wit GM, Verhaagen J. Anatomy of rat semaphorin III/collapsin-1 mRNA expression and relationship to developing nerve tracts during neuroembryogenesis. J Comp Neurol (1996) 375:378-92.
35. de Castro F, Hu L, Drabkin H, Sotelo C, Chedotal A. Chemoattraction and chemorepulsion of olfactory bulb axons by different secreted semaphorins. J Neurosci (1999) 19:4428-36.
36. Giger RJ, Cloutier JF, Sahay A, Prinjha RK, Levengood DV, Moore SE, et al. Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins. Neuron (2000) 25:29-41. doi:10.1016/S0896-6273(00)80869-7.
37. Schwarting GA, Kostek C, Ahmad N, Dibble C, Pays L, Puschel AW. Semaphorin 3A is required for guidance of olfactory axons in mice. J Neurosci (2000) 20:7691-7.
38. Cloutier JF, Giger RJ, Koentges G, Dulac C, Kolodkin AL, Ginty DD. Neuropilin-2 mediates axonal fasciculation, zonal segregation, but not axonal convergence, of primary accessory olfactory neurons. Neuron (2002) 33:877-92. doi:10.1016/S0896-6273(02)00635-9.
39. Pasterkamp RJ, Kolk SM, Hellemons AJ, Kolodkin AL. Expression patterns of semaphorin7A and plexinC1 during rat neural development suggest roles in axon guidance and neuronal migration. BMC Dev Biol (2007) 7:98. doi:10.1186/1471-213X-7-98.
40. Messina A, Ferraris N, Wray S, Cagnoni G, Donohue DE, Casoni F, et al. Dysregulation of Semaphorin7A/beta1-integrin signaling leads to defective GnRH-1 cell migration, abnormal gonadal development and altered fertility. Hum Mol Genet (2011) 20:4759-74. doi:10.1093/hmg/ddr403.
41. Ebert AM, Lamont RE, Childs SJ, McFarlane S. Neuronal expression of class 6 semaphorins in zebrafish. Gene Expr Patterns (2012) 12:117-22. doi:10.1016/j.gep.2012.01.007.
42. Elhabazi A, Delaire S, Bensussan A, Boumsell L, Bismuth G. Biological activity of soluble CD100. I. The extracellular region of CD100 is released from the surface of T lymphocytes by regulated proteolysis. J Immunol (2001) 166:4341-7.
43. Wang X, Kumanogoh A, Watanabe C, Shi W, Yoshida K, Kikutani H. Functional soluble CD100/Sema4D released from activated lymphocytes:possible role in normal and pathologic immune responses. Blood (2001) 97:3498-504. doi:10.1182/blood. V97.11.3498.
44. Swiercz JM, Kuner R, Behrens J, Offermanns S. Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology. Neuron (2002) 35:51-63. doi:10.1016/S0896-6273(02)00750-X.
45. Conrotto P, Corso S, Gamberini S, Comoglio PM, Giordano S. Interplay between scatter factor receptors and B plexins controls invasive growth. Oncogene (2004) 23:5131-7. doi:10.1038/sj.onc.1207650.
46. Geller S, Kolasa E, Tillet Y, Duittoz A, Vaudin P. Olfactory ensheathing cells form the microenvironment of migrating GnRH-1 neurons during mouse development. Glia (2013) 61:550-66. doi:10.1002/glia.22455.
47. Dacquin R, Domenget C, Kumanogoh A, Kikutani H, Jurdic P, Machuca-Gayet I. Control of bone resorption by semaphorin 4D is dependent on ovarian function. PLoS ONE (2011) 6:e26627. doi:10.1371/journal.pone.0026627.
48. Jongbloets BC, Ramakers GM, Pasterkamp RJ. Semaphorin7A and its receptors:pleiotropic regulators of immune cell function, bone homeostasis, and neural development. Semin Cell Dev Biol (2013) 24:129-38. doi:10.1016/j.semcdb.2013.01.002.
49. Scott GA, McClelland LA, Fricke AF. Semaphorin 7a promotes spreading and dendricity in human melanocytes through beta1-integrins. J Invest Dermatol (2008) 128:151-61. doi:10.1038/sj.jid.5700974.
50. Lazova R, Gould Rothberg BE, Rimm D, Scott G. The semaphorin 7A receptor Plexin C1 is lost during melanoma metastasis. Am J Dermatopathol (2009) 31:177-81. doi:10.1097/DAD.0b013e318196672d.
51. Scott GA, McClelland LA, Fricke AF, Fender A. Plexin C1, a receptor for semaphorin 7a, inactivates cofilin and is a potential tumor suppressor for melanoma progression. J Invest Dermatol (2009) 129:954-63. doi:10.1038/jid.2008.329.
52. Ohsawa S, Hamada S, Asou H, Kuida K, Uchiyama Y, Yoshida H, et al. Caspase-9 activation revealed by semaphorin 7A cleavage is independent of apoptosis in the aged olfactory bulb. J Neurosci (2009) 29:11385-92. doi:10.1523/JNEUROSCI.4780-08.2009.
53. Ohsawa S, Hamada S, Kuida K, Yoshida H, Igaki T, Miura M. Maturation of the olfactory sensory neurons by Apaf-1/caspase-9-mediated caspase activity. Proc Natl Acad Sci U S A (2010) 107:13366-71. doi:10.1073/pnas.0910488107.
54. Fukunishi A, Maruyama T, Zhao H, Tiwari M, Kang S, Kumanogoh A, et al. The action of Semaphorin7A on thalamocortical axon branching. J Neurochem (2011) 118:1008-15. doi:10.1111/j.1471-4159.2011.07390.x.
55. Parkash J, Cimino I, Ferraris N, Casoni F, Wray S, Cappy H, et al. Suppression of beta1-integrin in gonadotropin-releasing hormone cells disrupts migration and axonal extension resulting in severe reproductive alterations. J Neurosci (2012) 32:16992-7002. doi:10.1523/JNEUROSCI.3057-12.2012.
56. Simerly RB. Wired for reproduction:organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci (2002) 25:507-36. doi:10.1146/annurev.neuro.25.112701.142745.
57. Tobet S, Knoll JG, Hartshorn C, Aurand E, Stratton M, Kumar P, et al. Brain sex differences and hormone influences:a moving experience? J Neuroendocrinol (2009) 21:387-92. doi:10.1111/j.1365-2826.2009.01834.x.
58. Yu HH, Houart C, Moens CB. Cloning and embryonic expression of zebrafish neuropilin genes. Gene Expr Patterns (2004) 4:371-8. doi:10.1016/j.modgep.2004.01.011.
59. Murakami Y, Suto F, Shimizu M, Shinoda T, Kameyama T, Fujisawa H. Differential expression of plexin-A subfamily members in the mouse nervous system. Dev Dyn (2001) 220:246-58. doi:10.1002/1097-0177(20010301)220:3<246::AID-DVDY1112>3.0.CO;2-2.
60. Cariboni A, Hickok J, Rakic S, Andrews W, Maggi R, Tischkau S, et al. Neuropilins and their ligands are important in the migration of gonadotropin-releasing hormone neurons. J Neurosci (2007) 27:2387-95. doi:10.1523/JNEUROSCI.5075-06.2007.
61. Walz A, Rodriguez I, Mombaerts P. Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice. J Neurosci (2002) 22:4025-35.
62. Pasterkamp RJ, De Winter F, Holtmaat AJ, Verhaagen J. Evidence for a role of the chemorepellent semaphorin III and its receptor neuropilin-1 in the regeneration of primary olfactory axons. J Neurosci (1998) 18:9962-76.
63. Imai T, Yamazaki T, Kobayakawa R, Kobayakawa K, Abe T, Suzuki M, et al. Pre-target axon sorting establishes the neural map topography. Science (2009) 325:585-90. doi:10.1126/science.1173596.
64. Cariboni A, Davidson K, Dozio E, Memi F, Schwarz Q, Stossi F, et al. VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels. Development (2011) 138:3723-33. doi:10.1242/dev.063362.
65. Cariboni A, Davidson K, Rakic S, Maggi R, Parnavelas JG, Ruhrberg C. Defective gonadotropin-releasing hormone neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2:implications for the aetiology of hypogonadotropic hypogonadism. Hum Mol Genet (2011) 20:336-44. doi:10.1093/hmg/ddq468.
66. Hanchate NK, Giacobini P, Lhuillier P, Parkash J, Espy C, Fouveaut C, et al. SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. PLoS Genet (2012) 8:e1002896. doi:10.1371/journal.pgen.1002896.
67. Schwanzel-Fukuda M, Bick D, PfaffDW. Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome. Brain Res Mol Brain Res (1989) 6:311-26. doi:10.1016/0169-328X(89)90076-4.
68. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell (1998) 92:735-45. doi:10.1016/S0092-8674(00)81402-6.
69. Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G. Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165. J Biol Chem (2000) 275:18040-5. doi:10.1074/jbc. M909259199.
70. Karpanen T, Heckman CA, Keskitalo S, Jeltsch M, Ollila H, Neufeld G, et al. Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. FASEB J (2006) 20:1462-72. doi:10.1096/fj.05-5646com.
71. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (1983) 219:983-5. doi:10.1126/science.6823562.
72. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science (1989) 246:1306-9. doi:10.1126/science.2479986.
73. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature (1996) 380:435-9. doi:10.1038/380435a0.
74. Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O'Shea KS, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature (1996) 380:439-42. doi:10.1038/380439a0.
75. Fantin A, Maden CH, Ruhrberg C. Neuropilin ligands in vascular and neuronal patterning. Biochem Soc Trans (2009) 37:1228-32. doi:10.1042/BST0371228.
76. Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J Neurosci (1999) 19:5731-40.
77. Oosthuyse B, Moons L, Storkebaum E, Beck H, Nuyens D, Brusselmans K, et al. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet (2001) 28:131-8. doi:10.1038/88842.
78. Ogunshola OO, Antic A, Donoghue MJ, Fan SY, Kim H, Stewart WB, et al. Paracrine and autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system. J Biol Chem (2002) 277:11410-5. doi:10.1074/jbc. M111085200.
79. Gu C, Rodriguez ER, Reimert DV, Shu T, Fritzsch B, Richards LJ, et al. Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev Cell (2003) 5:45-57. doi:10.1016/S1534-5807(03)00169-2.
80. de Roux N, Young J, Misrahi M, Genet R, Chanson P, Schaison G, et al. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med (1997) 337:1597-602.
81. Mitchell AL, Dwyer A, Pitteloud N, Quinton R. Genetic basis and variable phenotypic expression of Kallmann syndrome:towards a unifying theory. Trends Endocrinol Metab (2011) 22:249-58. doi:10.1016/j.tem.2011.03.002.
82. Bonomi M, Libri DV, Guizzardi F, Guarducci E, Maiolo E, Pignatti E, et al. New understandings of the genetic basis of isolated idiopathic central hypogonadism. Asian J Androl (2012) 14:49-56. doi:10.1038/aja.2011.68.
83. Pingault V, Bodereau V, Baral V, Marcos S, Watanabe Y, Chaoui A. Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness. Am J Hum Genet (2013) 92:707-24. doi:10.1016/j.ajhg.2013.03.024.
84. Balasubramanian R, Crowley WF Jr. Isolated GnRH deficiency:a disease model serving as a unique prism into the systems biology of the GnRH neuronal network. Mol Cell Endocrinol (2011) 346:4-12. doi:10.1016/j.mce.2011.07.012.
85. Dode C, Hardelin JP. Kallmann syndrome. Eur J Hum Genet (2009) 17:139-46. doi:10.1038/ejhg.2008.206.
86. Sykiotis GP, Plummer L, Hughes VA, Au M, Durrani S, Nayak-Young S, et al. Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. Proc Natl Acad Sci U S A (2010) 107:15140-4. doi:10.1073/pnas.1009622107.
87. Young J, Metay C, Bouligand J, Tou B, Francou B, Maione L, et al. SEMA3A deletion in a family with Kallmann syndrome validates the role of semaphorin 3A in human puberty and olfactory system development. Hum Reprod (2012) 27:1460-5. doi:10.1093/humrep/des022.
88. Lalani SR, Safiullah AM, Molinari LM, Fernbach SD, Martin DM, Belmont JW. SEMA3E mutation in a patient with CHARGE syndrome. J Med Genet (2004) 41:e94. doi:10.1136/jmg.2003.017640.
89. Kim HG, Layman LC. The role of CHD7 and the newly identified WDR11 gene in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Mol Cell Endocrinol (2011) 346:74-83. doi:10.1016/j.mce.2011.07.013.
90. Kim HG, Kurth I, Lan F, Meliciani I, Wenzel W, Eom SH, et al. Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet (2008) 83:511-9. doi:10.1016/j.ajhg.2008.09.005.
91. Carmeliet P, Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature (2005) 436:193-200. doi:10.1038/nature03875.
92. Larrivee B, Freitas C, Suchting S, Brunet I, Eichmann A. Guidance of vascular development:lessons from the nervous system. Circ Res (2009) 104:428-41. doi:10.1161/CIRCRESAHA.108.188144.
93. Makita T, Sucov HM, Gariepy CE, Yanagisawa M, Ginty DD. Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons. Nature (2008) 452:759-63. doi:10.1038/nature06859.
94. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci (2004) 5:347-60. doi:10.1038/nrn1387.
95. Pasterkamp RJ, Giger RJ. Semaphorin function in neural plasticity and disease. Curr Opin Neurobiol (2009) 19:263-74. doi:10.1016/j.conb.2009.06.001.
96. Serini G, Valdembri D, Zanivan S, Morterra G, Burkhardt C, Caccavari F, et al. Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature (2003) 424:391-7. doi:10.1038/nature01946.
97. Prevot V, Hanchate NK, Bellefontaine N, Sharif A, Parkash J, Estrella C, et al. Function-related structural plasticity of the GnRH system:a role for neuronal-glial-endothelial interactions. Front Neuroendocrinol (2010) 31:241-58. doi:10.1016/j.yfrne.2010.05.003.
98. Page R. The anatomy of the hypothalamo-hypophysial complex. In:Knobil E, Neill JD, editors. Physiology of Reproduction. New York:Raven Press (1994). p. 1527-619.
99. Prevot V, Bellefontaine N, Baroncini M, Sharif A, Hanchate NK, Parkash J, et al. Gonadotrophin-releasing hormone nerve terminals, tanycytes and neurohaemal junction remodelling in the adult median eminence:functional consequences for reproduction and dynamic role of vascular endothelial cells. J Neuroendocrinol (2010) 22:639-49. doi:10.1111/j.1365-2826.2010.02033.x.
100. Bellefontaine N, Hanchate NK, Parkash J, Campagne C, de Seranno S, Clasadonte J, et al. Nitric oxide as key mediator of neuron-to-neuron and endothelia-to-glia communication involved in the neuroendocrine control of reproduction. Neuroendocrinology (2011) 93:74-89. doi:10.1159/000324147.
101. Campagne C, Bouret SG, Leroy D, Beauvillain J-C, Prevot V. Semaphorin3A may be a chemotropic factor used by endothelial cells of the median eminence to regulate GnRH axon plasticity during the rat estrous cycle. In:Abstracts of the 38th Annual Meeting of the Society for Neuroscience (No. 618.3). Washington, DC (2008).
102. Parkash J, Loyens A, Gallet S, Balland E, Pralong F, Pasterkamp RJ, et al. Semaphorin 7A expression in tanycytes is regulated by sex-steroid hormones and controls gonadotropin-releasing hormone-1 (GnRH-1) cell plasticity. In:Abstracts of the 41st Annual Meeting of the Society for Neuroscience (No. 500.09), Washington, DC (2011).
103. Regev A, Goldman S, Shalev E. Semaphorin-4D (Sema-4D), the Plexin-B1 ligand, is involved in mouse ovary follicular development. Reprod Biol Endocrinol (2007) 5:12. doi:10.1186/1477-7827-5-12.
104. Negishi-Koga T, Shinohara M, Komatsu N, Bito H, Kodama T, Friedel RH, et al. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nat Med (2011) 17:1473-80. doi:10.1038/nm.2489.
105. Pavelock K, Braas K, Ouafik L, Osol G, May V. Differential expression and regulation of the vascular endothelial growth factor receptors neuropilin-1 and neuropilin-2 in rat uterus. Endocrinology (2001) 142:613-22. doi:10.1210/en.142.2.613.
106. Joseph D, Ho SM, Syed V. Hormonal regulation and distinct functions of semaphorin-3B and semaphorin-3F in ovarian cancer. Mol Cancer (2010) 9:499-509. doi:10.1158/1535-7163.MCT-09-0664.
107. Nguyen H, Ivanova VS, Kavandi L, Rodriguez GC, Maxwell GL, Syed V. Progesterone and 1,25-dihydroxyvitamin D inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F. Mol Cancer Res (2011) 9:1479-92. doi:10.1158/1541-7786.MCR-11-0213.
108. Yamauchi K, Mizushima S, Tamada A, Yamamoto N, Takashima S, Murakami F. FGF8 signaling regulates growth of midbrain dopaminergic axons by inducing semaphorin 3F. J Neurosci (2009) 29:4044-55. doi:10.1523/JNEUROSCI.4794-08.2009.
109. Kang HR, Lee CG, Homer RJ, Elias JA. Semaphorin 7A plays a critical role in TGF-beta1-induced pulmonary fibrosis. J Exp Med (2007) 204:1083-93. doi:10.1084/jem.20061273.