Gonadotropin-releasing hormone (GnRH) neurons involved in controlling the reproductive function in vertebrates are derived from the olfactory placode. However, in the sheep and the rat species, GnRH-immunoreactive (GnRH-IR) neurons could not be detected in the olfactory region during the earliest phase of GnRH system development. Using in situ hybridization (ISH) and immunohistochemistry (IHC) in sheep embryos ranging from 26 to 53 days’ gestational age (G26–G53), the present work confirmed that GnRH expression could not be detected during the earliest steps of migration. The first ISH+ cells were detected in the nasal septum and at the entrance of the telencephalon at G33 stage. [3H]-thymidine pulses applied to in vitro olfactory explant cultures showed that GnRH neuron precursor cells have an extended multiplication period corresponding to G26–G36 before entering the neuronal differentiation process. Therefore, the lack of GnRH neuron detection during the early phase of development in the sheep compared to the mouse and other vertebrates represents a major difference in the early development of GnRH neurons. In the mouse, GnRH neuron precursors have a limited multiplication period in the vomeronasal pit and only postmitotic neurons start migration, whereas in the sheep embryo, the multiplication period is extended to about 10 days as demonstrated in olfactory explant cultures.

1.
Schwanzel-Fukuda M, Pfaff DW: Origin of luteinizing hormone-releasing hormone neurons. Nature 1989;338:161–164.
2.
Wray S, Nieburgs A, Elkabes S: Spatiotemporal cell expression of luteinizing hormone-releasing hormone in the prenatal mouse: Evidence for an embryonic origin in the olfactory placode. Dev Brain Res 1989;46:309–318.
3.
Norgren RB, Lehman MN: Neurons that migrate from the olfactory epithelium in the chick express luteinizing hormone-releasing hormone. Endocrinology 1991;128:1676–1678.
4.
Sullivan KA, Silverman AJ: The ontogeny of gonadotropin-releasing hormone neurons in the chick. Neuroendocrinology 1993;58:597–608.
5.
Muske LE, Moore FL: The nervus terminalis in amphibians: Anatomy, chemistry and relationship with the hypothalamic gonadotropin-releasing hormone system. Brain Behav Evol 1988;32:141–150.
6.
Murakami S, Kikuyama S, Arai Y: The origin of the luteinizing hormone-releasing hormone neurons in newts (Cynops pyrrhogaster): The effect of olfactory placode ablation. Cell Tissue Res 1992;269–21–27.
7.
Ronnekleiv OK, Resko JA: Ontogeny of gonadotropin-releasing hormone-containing neurons in early fetal development of rhesus macaques. Endocrinology 1990;126:498–511.
8.
Quanbeck C, Sherwood NM, Millar RP, Terasawa E: Two populations of luteinizing hormone-releasing hormone neurons in the forebrain of the rhesus macaque during embryonic development. J Comp Neurol 1997;380:293–309.
9.
Jennes L: Prenatal development of the gonadotropin-releasing hormone-containing systems in rat brain. Brain Res 1989;482:97–108.
10.
Caldani M, Antoine M, Batailler M, Duittoz A: Ontogeny of GnRH systems. J Reprod Fertil Suppl 1995;49:147–162.
11.
Duittoz AH, Batailler M, Caldani M: Primary cell culture of LHRH neurons from embryonic olfactory placode in the sheep (Ovis aries). J Neuroendocrinol 1997;9:669–675.
12.
Koike I, Daikoku S: In vitro analysis of the centripetal migration mechanisms of developing LHRH neurons. Arch Histol Cytol 1995;58:265–283.
13.
Daikoku-Ishido H, Okamura Y, Yanaihara N, Daikoku S: Development of the hypothalamic luteinizing hormone-releasing hormone-containing neuron system in the rat: In vivo and transplantation studies. Dev Biol 1990;140:374–387.
14.
Caldani M, Batailler M, Thiéry JC, Dubois MP: LHRH-immunoreactive structures in the sheep brain. Histochemistry 1988;89:129–139.
15.
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.
16.
Bruneau G, Tillet Y: Localization of the preprosomatostatin-mRNA by in situ hybridization in the ewe hypothalamus. Peptides 1998;19:1749–1758.
17.
Cappello P, Tarozzo G, Benedetto A, Fasolo A: Proliferation and apoptosis in the mouse vomeronasal organ during ontogeny. Neurosci Lett 1999;266:37–40.
18.
Weiler E, McCulloch MA, Farbman AI: Proliferation in the vomeronasal organ of the rat during postnatal development. Eur J Neurosci 1999;11:700–711.
19.
Osada T, Ikai A, Costanzo RM, Matsuoka M, Ichikawa M: Continual neurogenesis of vomeronasal neurons in vitro. J Neurobiol 1999;40:226–233.
20.
Mulrenin EM, Witkin JW, Silverman AJ: Embryonic development of the gonadotropin-releasing hormone (GnRH) system in the chick: A spatio-temporal analysis of GnRH neuronal generation, site of origin, and migration. Endocrinology 1999;140:422–433.
21.
Kramer P, Wray S: Midline nasal tissue influences nestin expression in nasal-placode-derived luteinizing hormone-releasing hormone neurons during development. Dev Biol 2000;227:343–357.
22.
Wu TJ, Gibson MJ, Silverman AJ: Gonadotropin-releasing hormone neurons in the developing tectum of the mouse. J Neuroendocrinol 1995;7:899–902.
23.
Simonian SX, Herbison AE: Regulation of gonadotropin-releasing hormone (GnRH) gene expression during GnRH neuron migration in the mouse. Neuroendocrinology 2001;73:149–156.
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