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Biomedical subjects

M Schwanzel-Fukuda

Publications and source records attributed to M Schwanzel-Fukuda.

At least 19 recordsLinked to original sources
PubMed1999

Origin and migration of luteinizing hormone-releasing hormone neurons in mammals.

Luteinizing hormone-releasing hormone (LHRH) neurons are unique among hypothalamic neurons in that they originate outside of the central nervous system. In most vertebrates, LHRH-immunoreactive (-ir) neurons are detected in the epithelium of the medial olfactory pit soon after its formation. The LHRH-ir neurons migrate out of the placodal epithelium and into the brain along a migration route that consists of the central processes of the terminal, olfactory, and vomeronasal nerves. LHRH-ir cell migration follows a highly ordered course from the initial appearance of the LHRH-ir cells in the epithelium of the medial olfactory pit, to the crossing of these cells in cords on the nasal septum, to their entrance into the forebrain. Here they separate and follow an arching trajectory to their final destinations in the septal and preoptic areas and in the hypothalamus. Examination of the molecular makeup of the developing migration route reveals the presence of neural cell adhesion molecule (N-CAM) in non-LHRH-ir cells. The N-CAM-ir cells migrate into the nasal mesenchyme, trailed by N-CAM-ir axons of the olfactory, vomeronasal, and terminal nerves. These N-CAM cells and axons link the olfactory epithelia with the developing forebrain and together form scaffolding along which the LHRH-ir cells migrate into the brain. The focus of this review is on the origin and migration of LHRH-ir neurons in mammals, including humans. A discussion of Kallmann's syndrome (hypogonadotropic hypogonadism with anosmia) is included, in which there is an absence of LHRH-ir in the brain but clusters of LHRH-ir cells in the nasal cavity. This "experiment of nature" lends support to the hypothesis that all LHRH-ir cells in humans originate in the olfactory placode.

Animals↗
PubMed1999

Anosmin-1 is a regionally restricted component of basement membranes and interstitial matrices during organogenesis: implications for the developmental anomalies of X chromosome-linked Kallmann syndrome.

Kallmann syndrome is a developmental disease characterized by gonadotropin-releasing hormone (GnRH) deficiency and olfactory bulb hypoplasia. The gene underlying the X chromosome-linked form, KAL-1, has been identified for several years, yet the pathogenesis of the disease is not understood. By immunohistofluorescence and immunoelectron microscopy, we establish that the KAL-1 encoded protein, anosmin-1, is a transient and regionally restricted component of extracellular matrices during organogenesis in man. Anosmin-1 was detected in the basement membranes and/or interstitial matrices of various structures including bronchial tubes, mesonephric tubules and duct, branches of the ureteric bud, muscular walls of the digestive tract and larger blood vessels, precartilaginous models of skeletal pieces, muscle tendons, head mesenchymes, inner ear, and forebrain subregions. Our results suggest that this protein acts as a local, rather than a long-range, cue during organogenesis. In the olfactory system, anosmin-1 was detected from week 5 onward. The protein was restricted to the olfactory bulb presumptive region and later, to the primitive olfactory bulbs. We therefore suggest that the genetic defect underlying X-linked Kallmann syndrome disrupts the terminal navigation of the early olfactory axons or directly affects the initial steps of olfactory bulb differentiation. The mechanism of the GnRH deficiency is also discussed, relying on the evidence that anosmin-1 is present in the medial walls of the primitive cerebral hemispheres, along the rostro-caudal migratory pathway of the GnRH-synthesizing neurons, at 6 weeks. Finally, the present results strongly suggest that the renal aplasia observed in about one third of the affected individuals results from primary failure of the collecting duct system.

Basement Membrane↗
PubMed1998

Olfactory bulb development is altered in small-eye (Sey) mice.

Small-eye (Sey) is a spontaneous, semidominant murine mutation that results from a point mutation in the Pax-6 gene. Both the eyes and the olfactory system fail to develop in homozygotes and these animals die neonatally. Heterozygotes (Sey/+) have different degrees of eye abnormalities including decreased lens size and cataracts. In the present study, we examined whether one mutated allele of Pax-6 also affects olfactory system development. By 42 days of age, main olfactory bulb volume was significantly decreased in Sey/+ animals compared with wild-type littermates, and this effect was even more dramatic in 70-day-old animals. In contrast, there was no effect on accessory olfactory bulb, olfactory epithelial, or vomeronasal organ development at any age in Sey/+ animals, demonstrating the specificity of the effect. In the main olfactory bulb, the largest differences in laminar volume were found in the glomerular and granule cell layers. These layers contain the olfactory bulb interneurons, and a subpopulation of these cells were found to be Pax-6 immunoreactive. Examination of the neurochemical consequences of this mutation showed that the number of both tyrosine hydroxylase (TH)- and gamma-aminobutyric acid (GABA)-immunoreactive profiles were dramatically decreased in Sey/+ animals as compared with controls. In contrast, neither calretinin nor calbindin immunoreactivity was affected by this mutation. Dual-labeling immunohistochemistry showed that nearly all TH-immunoreactive cells and a subpopulation of GABA-immunoreactive cells coexpressed Pax-6. However, calretinin- and calbindin-immunoreactive cells were not Pax-6 immunopositive. These data indicate that two normal alleles of Pax-6 are required for normal olfactory bulb development and, as part of this effect, this gene may be involved in the development of specific neurotransmitter systems.

Aging↗
PubMed1998

The gonadotropin-releasing hormone system does not develop in Small-Eye (Sey) mouse phenotype.

This study examined the development of the gonadotropin releasing-hormone (GnRH) system in a spontaneous mouse mutation, Small-Eye (Sey). This phenotype is due to a point mutation in the developmental control gene Pax-6 and results in failed development of the eye and olfactory placodes in homozygous (Sey/Sey) embryos and a variety of eye abnormalities in heterozygotes (Sey/+). Therefore, Sey/Sey embryos provided a naturally occurring olfactory placode ablation to ask whether all of the GnRH neurons found in the adult mouse forebrain arise from the olfactory epithelium. In Sey/Sey embryos, GnRH-immunoreactive neurons were not present in either the presumptive nasal regions or in any area of the brain at any embryonic age. In contrast, in Sey/+ embryos, there was no apparent effect on either GnRH cell proliferation or migration. These data support and extend the hypothesis that GnRH neurons in mice originate in the olfactory placodes and also demonstrate that two normal alleles of Pax-6 are not required for GnRH system development.

Alleles↗
PubMed1998

Aspects of GnRH neurobiology conserved across vertebrate forms.

The decapeptide gonadotropin-releasing hormone (GnRH) came into prominence because of its roles in releasing luteinizing hormone and follicle-stimulating hormone and promoting reproductive behavior. At least three aspects of GnRH neurobiology have features which may be universal among vertebrates. First, the GnRH neuronal migration from the olfactory placode into the basal forebrain appears to hold true for forms ranging from fish to humans. Second, for proper agonist activity in the anterior pituitary, GnRH must be released in a pulsatile fashion. Since GT-1 neuronal cell cultures can demonstrate pulsatile release, it must be concluded that GnRH neuronal networks themselves can manage this type of pulsatility. Using a neuronal mathematical model with "minimalist" assumptions, we demonstrated that a network of identical neurons can achieve this self-organizing property without the use of, or spontaneous appearance of, "pacemaker cells." Indeed, since many parameter combinations worked, and since no information about species identity or chemical cell type is provided to the model, this conclusion could apply across many vertebrate forms and, perhaps, even for other neuroendocrine cell types. Third, Fernald and colleagues (this issue of General and Comparative Endocrinology) have demonstrated remarkable effects of social context on GnRH expression in fish. Reviewed here are some data in musk shrews suggesting that behavioral and social stimuli can also modify GnRH neurons in mammals. Therefore, although GnRH neuronal mechanisms are adapted to meet species-typical variations in environment and physiology, some of the important features of this system appear to be widely conserved.

Animals↗
PubMed1996

Gonadotropin-releasing hormone gene expression in teleosts.

Expression of multiple molecular forms of gonadotropin-releasing hormone (GnRH) mRNAs and GnRH peptides were examined in the brains of tilapia (Oreochromis mossambicus) and sockeye salmon (Oncorhynchus nerka), using in situ hybridization histochemistry and immunohistochemical techniques. After otherwise identical conditions, lesser background and stronger GnRH hybridization signals were observed on cryostat vs. paraffin sections. In both fresh and Bouin's-fixed paraffin-embedded tissues, there was a good correlation between the distribution of GnRH mRNA and GnRH peptide-containing cells. Although the brains of tilapia and the sockeye were immunoreactive to three forms of the GnRH molecule (salmon, mammal, chicken-II), GnRH mRNA expression was site-specific and species-specific. In the tilapia, ganglionic cells of the nucleus olfactoretinalis, basal telencephalon and the anteroventral preoptic area were immunoreactive to salmon-, and mammalian-GnRH peptide. Neurons of the nucleus olfactoretinalis expressed cichlid-GnRH I mRNA. The preoptic neurons, despite the immunoreactivity, expressed no hybridization signals. Midbrain neurons were immunoreactive to salmon-GnRH but expressed cichlid-GnRH II beta (= chicken-GnRH II) mRNA hybridization signals. In the sockeye, ganglionic cells along the extracerebral course of the nervus terminalis were immunoreactive to mammalian-, chicken-II and salmon-GnRH. These neurons expressed only salmon-GnRH mRNA hybridization signals. Intracerebral GnRH expression in the sockeye was delayed till smoltification. The basal telencephalon and midbrain neurons immunoreactive to salmon-GnRH, formed no hybridization signals with GnRH antisense probes. Oligonucleotide probes complementary to chicken-GnRH I and mammalian-GnRH revealed no hybridization signals in the tilapia and in the sockeye brain. Fibers, immunoreactive to salmon-, mammalian-, and chicken II-GnRH were seen in close association with growth hormone cells. Chicken-GnRH II-immunoreactive fibers were also seen in close proximity to somatolactin cells in the sockeye salmon.

Animals↗
PubMed1996

Migration of luteinizing hormone-releasing hormone (LHRH) neurons in early human embryos.

Luteinizing hormone-releasing hormone (LHRH) neurons originate in the epithelium of the medial olfactory pit and migrate from the nose into the forebrain along nerve fibers rich in neural cell adhesion molecule (N-CAM). The present study examined the ontogenesis of LHRH neurons in early human embryos and found a similar pattern of development of these cells. Luteinizing hormone-releasing hormone immunoreactivity was detected in the epithelium of the medial olfactory pit and in cells associated with the terminal-vomeronasal nerves at 42 (but not 28-32) days of gestation. The migration route of these cells was examined with antibodies to N-CAM and antibodies to polysialic acid (PSA-N-CAM), which is present on N-CAM at certain stages of development. Neural cell adhesion molecule immunoreactivity was present in a population of cells in the olfactory placode of the earliest embryos examined (28-32 days) and later (42 and 46 days) throughout the migration route. The PSA-N-CAM immunoreactivity was not detected until 42 days and was present in a more limited distribution in nerve fibers streaming from the olfactory placode and along the caudal part of the migration route below the forebrain. Previous studies have indicated that the highly sialated form of N-CAM is less adhesive. The PSA-N-CAM may therefore facilitate the migration of these cells by lessening the adhesion between the fascicles that make up the migration route, expediting the passage of cords of LHRH cells between the nerve fibers as these cells move toward the brain.

Antibodies, Monoclonal↗
PubMed1995

Embryonic development of gonadotropin-releasing hormone neurons in the sockeye salmon.

Immunocytochemistry and in situ hybridization were used to test the hypothesis that gonadotropin-releasing hormone (GnRH) neurons are formed in the olfactory placode during embryonic development in a salmonid, Oncorhynchus nerka. The development of GnRH neurons and the pituitary cell types was examined from 19 through 910 days after fertilization. Immunoreactive GnRH was first detected at 19 days in the cells of the olfactory placode. GnRH immunoreactivity was not detected in any other structure of the central nervous system at this age. By day 24, GnRH-immunoreactive neurons were seen in the apical, intermediate, and basal layers of the olfactory placode. From days 30 through 51, GnRH neurons were seen emerging from the epithelium, along the olfactory nerve, and at the rostral olfactory bulb. By day 41, GnRH immunoreactivity was lost in the nasal epithelium. In the 72-day-old fish, most of the GnRH neuronal population was found in ganglia of the nervus terminalis, at the cribriform bone (gCB), and at the rostral olfactory bulb (gROB). On day 293, a decrease in GnRH-immunoreactive neurons in the gCB and gROB was concomitant with an initial appearance of GnRH-immunoreactive neurons and fibers along the caudoventral olfactory bulb. By day 462, the distribution of GnRH neurons and fibers was almost similar to adults. In maturing adults (910 days), GnRH-immunoreactive neurons were rarely seen in the nasal regions, but were primarily found in the basal forebrain. GnRH fibers were widespread in the brain, proximal para distalis, and in the pars intermedia of the pituitary. Our study supports the notion that neurons expressing salmon-GnRH mRNA and peptide originate in the medial olfactory placode and migrate into the basal forebrain during development. The midbrain neurons did not express salmon-GnRH mRNA or peptide in the larval and juvenile fish.

Animals↗
PubMed1995

Genes and behavior as studied through gonadotropin-releasing hormone (GnRH) neurons: comparative and functional aspects.

1. GnRH neurons migrate from olfactory placode into the developing basal forebrain in a manner which appears remarkably constant across all vertebrates studied, from fish to human beings. 2. Interruption of this migration can result in Kallmann's Syndrome. Absence of libido by individuals suffering from Kallmann's has allowed us to chart a causal route from a specific gene to a human social behavior.

Aging↗
PubMed1994

Antibody to neural cell adhesion molecule can disrupt the migration of luteinizing hormone-releasing hormone neurons into the mouse brain.

The neurons which synthesize and release luteinizing hormone-releasing hormone (LHRH), are hypothesized to originate in the epithelium of the medial olfactory pit and to migrate into the brain along a scaffolding made up of neural cell adhesion molecule (NCAM)-immunoreactive branches of the terminal and vomeronasal nerves. These LHRH neurons, studied by immunocytochemical and autoradiographic procedures, were found to originate within a very short period of embryogenesis, specifically day 10, in mice, and to follow a remarkably ordered spatiotemporal course along the migration route into the brain. The purpose of the present experiments was to determine whether perturbation of the NCAM-immunoreactive migration route, at a particular time in development, would arrest the migration of LHRH neurons into the brain. We found that a 1 microliter injection of antiserum to NCAM into the area of the olfactory pit, on day 10 of embryogenesis, significantly reduced the number of LHRH-immunoreactive neurons seen in the epithelium of the medial olfactory pit, with a concomitant significant reduction in the number of LHRH-immunoreactive cells seen outside of the placode, on the migration route. These results confirm our initial hypothesis that LHRH neurons migrate from the epithelium of the olfactory pit to the brain and indicate that NCAM plays a causal role in this phenomenon.

Animals↗
PubMed1994

Luteinizing hormone-releasing hormone (LHRH) and neural cell adhesion molecule (NCAM)-immunoreactivity in development of the forebrain and reproductive system.

The origin and migration of LHRH neurons (detected by immunocytochemical procedures) is preceded by a migration of NCAM-immunoreactive cells from the olfactory epithelium, and the formation of an NCAM-immunoreactive cellular aggregate between the olfactory epithelium and the developing forebrain. The central processes of the olfactory nerves grow into the lateral parts of this aggregate and the terminal and vomeronasal nerves grow into the medial parts. No nerve fibers of the main or accessory olfactory systems grow directly into the forebrain. The LHRH neurons, following the course of the terminal and vomeronasal nerves, traverse the medial edge of the NCAM-immunoreactive cellular aggregate before they enter the medial forebrain caudal to the developing olfactory bulbs. The LHRH neurons do not migrate through the olfactory bulbs. After formation of the olfactory bulbs, the cellular aggregate disappears and is replaced by the olfactory nerve layer of the olfactory bulb. The NCAM and LHRH-immunoreactive cells on the medial side appear to the retained in the ganglion terminale of the terminal nerve. The fate of the NCAM-immunoreactive cells that formed the aggregate could not be determined by the methods used in these studies. The early-appearing NCAM-immunoreactive cells may function to separate and direct axons of the olfactory, vomeronasal and terminal nerves (and the LHRH neurons) to their respective targets in the forebrain. The development and migration of neurons from both the lateral and medial parts of the olfactory placode appears to be essential for the normal development of the forebrain and reproductive system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Differential OMP expression in opossum accessory olfactory bulb.

Using immunohistochemical techniques, olfactory marker protein (OMP) was localized to the main (MOB) and accessory (AOB) olfactory bulbs of 30- and 45-day-old, and adult Brazilian opossums, Monodelphis domestica. Entire olfactory nerve and glomerular layers of the adult opossum MOB were darkly stained. In the adult AOB the rostral half of these two layers was stained more intensely than the caudal half, and both parts were less darkly stained than the MOB. This differential AOB staining was not present at 30 days of age, but was evident by postnatal day 45, although not as dramatic as in adults. This is the first report of differential OMP expression and may provide an approach to identifying the function of OMP.

Aging↗
PubMed1992

Immunocytochemical demonstration of neural cell adhesion molecule (NCAM) along the migration route of luteinizing hormone-releasing hormone (LHRH) neurons in mice.

Contact between the developing forebrain and the ingrowing central processes of the olfactory, vomeronasal and terminal nerves is preceded by a migration of neural cell adhesion molecule (NCAM)-immunoreactive cells from the epithelium of the olfactory pit and the formation of an NCAM-immunoreactive cellular aggregate in the mesenchyme between the olfactory pit and the forebrain. The axons of the olfactory, vomeronasal, and terminal nerves, also NCAM-immunoreactive, grow into the cellular aggregate, which as development proceeds, becomes continuous with the rostral tip of the forebrain. The lateral and more rostral part of the cellular aggregate receives the ingrowing axons of the olfactory nerves and becomes the olfactory nerve layer of the olfactory bulb. The medial, more caudal part receives the central processes of the vomeronasal and terminal nerves. The vomeronasal nerve ends in the accessory olfactory bulb. The central processes of the terminal nerve end in the medial forebrain. Luteinizing hormone-releasing hormone (LHRH)-immunoreactive neurons, like the vomeronasal and terminal nerves, originate from the medial part of the olfactory pit. These LHRH cells migrate into the brain along and within a scaffolding formed by the NCAM-immunoreactive axons of the vomeronasal and terminal nerves, and they are never seen independent of this NCAM scaffold as they cross the nasal lamina propria. The results suggest that: (1) NCAM is likely to be necessary for scaffold formation, and (2) the scaffold may be essential for the subsequent migration of LHRH neurons into the brain. Because they aggregate, migrating LHRH-immunoreactive neurons, on which we did not detect NCAM immunoreactivity, may interact via other cell adhesion molecules (CAM). Inasmuch as the interaction between the LHRH-immunoreactive neurons and the NCAM-immunoreactive scaffold is heterotypic, the possibility of a heterophilic (NCAM to other CAM) interaction is not ruled out. These findings focus our attention on the functional role of NCAM in this migratory system.

Animals↗
PubMed1992

Electron microscopic identification of luteinizing hormone-releasing hormone-immunoreactive neurons in the medial olfactory placode and basal forebrain of embryonic mice.

Luteinizing hormone-releasing hormone is a decapeptide found in the brain and nose of all vertebrates that have been examined by immunocytochemical procedures with antiserum to luteinizing hormone-releasing hormone. It regulates the release of both luteinizing hormone and follicle-stimulating hormone from the gonadotropes of the anterior pituitary gland and promotes mating behavior. After about 11 days of embryogenesis in mice, luteinizing hormone-releasing hormone-immunoreactive cells are detected by immunocytochemical procedures in the medial olfactory placode, in the primordium of the vomeronasal organ. As they leave the olfactory placode, they run under the epithelial layer of the nasal septum associated with vomeronasal and terminalis nerves. Clustered, they stream toward the primordium of the olfactory bulb, passing along its ventromedial surface. Eventually, the largest numbers reach the septal and preoptic areas of the brain. Electron microscopic immunocytochemistry showed that luteinizing hormone-releasing hormone-immunoreactive product is accumulated just outside the nuclear envelope and in the lumen of rough endoplasmic reticulum adjacent to the cell nucleus of cells in and adjacent to the olfactory placode. As luteinizing hormone-releasing hormone-immunoreactive neurons migrate, they assume a fusiform shape and the immunoreaction product extends from the area around the nucleus throughout the cytoplasm, notably in processes which extend toward the direction of migration. Before and during migration, luteinizing hormone-releasing hormone was not detected in the Golgi apparatus or neurosecretory granules. It is inferred that as far as ultrastructural evidence is concerned, these neurons do not have a secretory function before they attain their target organs.

Animals↗
PubMed1992

LHRH neurons: functions and development.

Examination of the properties of developing LHRH neurons, by in situ hybridization procedures or LHRH immunocytochemistry, showed that these cells (1) are unique among neuroendocrine cells in their origin from the epithelium of the medial olfactory pit, and (2) express LHRH mRNA. LHRH neurons, visualized by either method, tended to be clustered when seen along the migration route in the nasal mesenchyme. Neural cell adhesion molecule (NCAM) is present on the central processes of the olfactory, vomeronasal and terminalis nerves, which form the scaffold along which LHRH neurons migrate into the brain. Injection of a small amount (1 microliter) of antiserum to NCAM into the olfactory pits of 10-day-old embryonic mice, while not sufficient to break up the NCAM scaffolding, appeared to decrease the number of LHRH-immunoreactive cells in the epithelium of the medial olfactory pit, and retarded their migration in the nasal mesenchyme. This suggest that NCAM is important for LHRH cell migration. Never found actually colocalized with LHRH in the same neurons, NCAM nevertheless may be required for the migration of LHRH-expressing cells.

Adult↗
PubMed1991

Migration of LHRH-immunoreactive neurons from the olfactory placode rationalizes olfacto-hormonal relationships.

Nerve cells that express luteinizing hormone-releasing hormone (LHRH), essential for reproductive functions, originate in the epithelium of the medial olfactory placode. While the peripheral origin of this physiologically important brain peptide is surprising, associations between olfactory and reproductive systems are well documented in behavioral studies of pheromones and in clinical studies of disorders including hypogonadotropic hypogonadism with anosmia or olfactory-genital dysplasia. Mechanisms underlying this migration include a close association with neural cell adhesion molecules (NCAM), but are likely also to involve other physical and chemical factors.

Animals↗