Reelin provides an inhibitory signal in the migration of gonadotropin-releasing hormone neurons

Cariboni, Anna; Rakić, Sonja; Liapi, Anastasia; Maggi, Roberto; Goffinet, André M.; Parnavelas, John G.

doi:10.1242/dev.02033

Cited by 70 publications

(80 citation statements)

References 68 publications

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“…GN11 cells show a strong chemomigratory response in vitro (Maggi et al, 2000) and, as such, they have been used to investigate mechanisms involved in GnRH neuron migration (Giacobini et al, 2002;Cariboni et al, 2004Cariboni et al, , 2005. We first performed expression studies on GN11 cells to confirm our in vivo observations.…”

Section: Semaphorins and Neuropilins Are Involved In The Migration Ofmentioning

confidence: 85%

“…Cell aggregates of GN11 cells were prepared by the "hanging drop" technique as described previously (Kennedy et al, 1994). Rat-tail collagen solution was prepared as described by Guthrie and Lumsden (1994), and collagen gels and GN11 cell aggregates were generated as described by Cariboni et al (2005). After collagen polymerization (30 min), the preparations were covered with 500 l of control or semaphorin-enriched CM and cultured in a humidified, 5% CO 2 , 37°C incubator.…”

Section: Methodsmentioning

confidence: 99%

“…Chemomigration assays were performed using a 48-well Boyden's chamber as described previously (Maggi et al, 2000;Cariboni et al, 2005). Different semaphorin CMs or control CM and recombinant VEGF forms [50 nM; mouse VEGF 164 (R & D Systems, Abingdon, UK) and rat VEGF-C (ReliaTech, Braunschweig, Germany)] were used as chemoattractants and placed into the lower compartment of the chamber.…”

Section: Methodsmentioning

confidence: 99%

“…As a source of semaphorins, we used CM of COS-7 cells transfected with Sema3A and Sema3F expression vectors (see Materials and Methods). We used aggregates of GN11 cells in a three-dimensional collagen gel as previously described (Cariboni et al, 2005). These aggregates were treated with either 1% FBS (positive control) or CM from untransfected or semaphorin (3A, 3F)-transfected COS cells.…”

Section: The Effects Of Semaphorins and Vegfs On The Migration Of Gnrmentioning

confidence: 99%

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Neuropilins and Their Ligands Are Important in the Migration of Gonadotropin-Releasing Hormone Neurons

Cariboni¹,

Hickok²,

Rakić³

et al. 2007

J. Neurosci.

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Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus play an important role in reproductive function. These cells originate in the nasal compartment and migrate into the basal forebrain in association with olfactory/vomeronasal nerves in embryonic life in rodents. Here, we studied the role of neuropilins and their ligands, semaphorins, in the development of the olfactory-GnRH system. We focused on Neuropilin-2 knock-out (Npn-2 ؊/؊ ) mice, because they are known to display defasciculation of olfactory nerves and reduced fertility. We found a significant decrease in the number of GnRH neurons in the hypothalamus and a marked reduction in their gonadal size. We then observed an abnormal increase of GnRH neurons in the noses of Npn-2 ؊/؊ mice, indicating that these cells failed to migrate into the forebrain. However, because neuropilins and semaphorins are involved in events of neuronal migration in the brain, we asked whether the observed reduction in GnRH neurons was directly attributable to the action of these molecules. Using fluorescenceactivated cell sorting and reverse transcription-PCR on mRNA derived from embryonic green fluorescent protein (GFP)-GnRH transgenic mice, we found expression of class 3 semaphorins and their receptors (neuropilin-1/2 and plexin-A1) in GnRH neurons. Furthermore, double-immunofluorescence experiments showed that migrating GnRH neurons, as well as associated olfactory fibers, express Npn-2 in the nasal region. We then used a line of immortalized GnRH neurons (GN11 cells) that display the same expression patterns for semaphorins and their receptors as GFP-GnRH cells and found that class 3 semaphorins and vascular endothelial growth factors modulate their migratory activity. These studies provide support for the direct involvement of neuropilins and their ligands in the establishment of the GnRH neuroendocrine system.

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Section: Semaphorins and Neuropilins Are Involved In The Migration Ofmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The Effects Of Semaphorins and Vegfs On The Migration Of Gnrmentioning

confidence: 99%

See 2 more Smart Citations

Neuropilins and Their Ligands Are Important in the Migration of Gonadotropin-Releasing Hormone Neurons

Cariboni¹,

Hickok²,

Rakić³

et al. 2007

J. Neurosci.

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“…Mutation of netrin 1 or DCC led to an impairment of the migration of GnRH neurons (Schwalting et al, 2001(Schwalting et al, , 2004 and projection of the GnRH axons to the median eminence, thereby predicting the malformation of the neuroendocrine axis (Diner and Sretavan, 1999). In addition, reelin, an extracellular matrix protein expressed in the olfactory system, has also been shown to affect the migration of GnRH neurons (Cariboni et al, 2005). The inhibitory effects of reelin on migrating GnRH neurons are implicated in regulating the disposition of these neurons in the olfactory bulb.…”

mentioning

confidence: 99%

Netrin 1 provides a chemoattractive cue for the ventral migration of GnRH neurons in the chick forebrain

Murakami

Ohki‐Hamazaki

Watanabe

et al. 2010

J of Comparative Neurology

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Hypothalamic gonadotropin-releasing hormone (GnRH) neurons originate in the olfactory placode and migrate to the forebrain during embryonic development. We found that GnRH neurons migrated in two different modes in the chick medial telencephalon: they initially underwent axophilic migration in association with a subset of olfactory fibers in a dorsocaudal direction. This was followed by ventrally directed tangential migration to the basal forebrain. Since many of the ventrally migrating GnRH neurons did not follow distinct fiber fascicles, it is proposed that diffusible guidance molecules played a role in this migratory process. A long-range diffusible factor, netrin 1, was expressed in the lower part of the commissural plate and the subpallial septum, but not along the axophilic migratory route of GnRH neurons. Failure of ventrally directed migration of GnRH neurons and their misrouting to the dorsomedial forebrain was induced by misexpression of netrin 1 in the dorsocaudal part of the septum near the top of the commissural plate, which is where the migration of GnRH neurons changed to a ventral direction. In such cases, a subset of olfactory fibers also extended, but close contact between aberrant fibers and misrouted GnRH neurons did not exist. A coculture experiment demonstrated that netrin 1 exerts an attractive effect on migrating GnRH neurons. These results provide evidence that netrin 1 acts as chemoattractant to migrating GnRH neurons at the dorsocaudal part of the septum and has the potential to regulate the ventral migration of GnRH neurons to the ventral septum and the preoptic area.

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Postoperative intensity‐modulated radiotherapy in sinonasal carcinoma

Duthoy

Boterberg

Claus

et al. 2005

Cancer

106

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BACKGROUNDCarcinoma of the paranasal sinuses is rare. Standard therapeutic modalities consist of surgery and radiotherapy (RT). Because of the often advanced stage and the vicinity of optic structures, RT‐induced ocular toxicity is a feared side effect of conventional RT. Intensity‐modulated radiotherapy (IMRT) is a relatively new technique, which is implemented with the hypothesis that, compared with conventional RT, it would result in a lower rate of ocular toxicity for an equal local control (LC).METHODSBetween 1998 and 2003, 39 consecutive patients received postoperative irradiation by means of IMRT for an adenocarcinoma (n = 31) or squamous cell carcinoma (n = 8) of the paranasal sinuses (n = 36) or nasal cavity (n = 3). T‐classification was T2 in 41%, T3 in 15%, T4a in 23%, and T4b in 21% of patients. Invasion through the cribriform plate was seen in 11 patients. Orbital invasion was present in 36% of patients. The median delivered dose was 70 gray (Gy) (range, 60–70 Gy). The authors compared the overall survival (OS) and LC of the patients with a historic cohort (HC) (n = 30), treated with conventional or 3‐dimensional conformal RT.RESULTSThe median follow‐up was 31 months. The actuarial OS rates were 68% at 2 years and 59% at 4 years. The actuarial LC rates were 73% at 2 years and 68% at 4 years. Invasion through the cribriform plate was a significant prognostic factor for LC and OS, with a median time to local disease recurrence of 7 months if present, and a 2‐year LC rate of 90% if not present. In the comparison between the IMRT and HC groups, no significant differences were found for LC and OS. Acute toxicity was mild. Two patients developed decreased vision after RT. No RT‐induced blindness was observed.CONCLUSIONSPostoperative IMRT for sinonasal carcinoma resulted in good LC, with a low acute toxicity and no RT‐induced blindness. Cancer 2005. © 2005 American Cancer Society.

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Reelin provides an inhibitory signal in the migration of gonadotropin-releasing hormone neurons

Cited by 70 publications

References 68 publications

Neuropilins and Their Ligands Are Important in the Migration of Gonadotropin-Releasing Hormone Neurons

Neuropilins and Their Ligands Are Important in the Migration of Gonadotropin-Releasing Hormone Neurons

Netrin 1 provides a chemoattractive cue for the ventral migration of GnRH neurons in the chick forebrain

Postoperative intensity‐modulated radiotherapy in sinonasal carcinoma

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