GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling
Gonadotropin releasing hormone-1 (GnRH-1) neurons play a pivotal role in controlling pubertal onset and fertility once they reach their hypothalamic location. During embryonic development, GnRH-1 neurons migrate from the nasal area to the hypothalamus where they modulate gonadotropin release from th...
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doaj-613c927406554dbaaaca0399ecd5dd782020-11-25T01:34:27ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-03-011310.3389/fncel.2019.00070441271GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 SignalingEd Zandro M. Taroc0Jennifer M. Lin1Alastair J. Tulloch2Alexander Jaworski3Paolo E. Forni4Department of Biological Sciences, University at Albany, Albany, NY, United StatesDepartment of Biological Sciences, University at Albany, Albany, NY, United StatesDepartment of Neuroscience, Brown University, Providence, RI, United StatesDepartment of Neuroscience, Brown University, Providence, RI, United StatesDepartment of Biological Sciences, University at Albany, Albany, NY, United StatesGonadotropin releasing hormone-1 (GnRH-1) neurons play a pivotal role in controlling pubertal onset and fertility once they reach their hypothalamic location. During embryonic development, GnRH-1 neurons migrate from the nasal area to the hypothalamus where they modulate gonadotropin release from the pituitary gland. Defective migration of the GnRH-1 neurons to the brain, lack of GnRH-1 secretion or signaling cause hypogonadotropic hypogonadism (HH), a pathology characterized by delayed or absence of puberty. Binding of the guidance cue Slit2 to the receptor roundabout 3 (Robo3) has been proposed to modulate GnRH-1 cell motility and basal forebrain (bFB) access during migration. However, evidence suggests that Neural EGFL Like 2 (NELL2), not Slit2, binds to Robo3. To resolve this discrepancy, we analyzed GnRH-1 neuronal migration in NELL2, Robo3, and Slit2 knock-out mouse lines. Our data do not confirm a negative effect for monogenic Robo3 and Slit2 mutations on GnRH-1 neuronal migration from the nasal area to the brain. Moreover, we found no changes in GnRH-1 neuronal migration in the brain after NELL2 loss-of-function. However, we found that Slit2 loss-of-function alters the patterning of GnRH-1 cells in the brain, suggesting that Slit2 loss-of-function affects GnRH-1 cell positioning in the brain in a Robo3 independent fashion. Our results challenge previous theories on GnRH-1 neuronal migration mechanisms and provide a new impetus to identify and understand the complex genetic mechanisms causing disorders like Kallmann syndrome (KS) and HH.https://www.frontiersin.org/article/10.3389/fncel.2019.00070/fullGnRH-1olfactory bulbsKallmann syndromehypogonadotropic hypogonadismneuronal migrationRobo |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ed Zandro M. Taroc Jennifer M. Lin Alastair J. Tulloch Alexander Jaworski Paolo E. Forni |
spellingShingle |
Ed Zandro M. Taroc Jennifer M. Lin Alastair J. Tulloch Alexander Jaworski Paolo E. Forni GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling Frontiers in Cellular Neuroscience GnRH-1 olfactory bulbs Kallmann syndrome hypogonadotropic hypogonadism neuronal migration Robo |
author_facet |
Ed Zandro M. Taroc Jennifer M. Lin Alastair J. Tulloch Alexander Jaworski Paolo E. Forni |
author_sort |
Ed Zandro M. Taroc |
title |
GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling |
title_short |
GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling |
title_full |
GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling |
title_fullStr |
GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling |
title_full_unstemmed |
GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling |
title_sort |
gnrh-1 neural migration from the nose to the brain is independent from slit2, robo3 and nell2 signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2019-03-01 |
description |
Gonadotropin releasing hormone-1 (GnRH-1) neurons play a pivotal role in controlling pubertal onset and fertility once they reach their hypothalamic location. During embryonic development, GnRH-1 neurons migrate from the nasal area to the hypothalamus where they modulate gonadotropin release from the pituitary gland. Defective migration of the GnRH-1 neurons to the brain, lack of GnRH-1 secretion or signaling cause hypogonadotropic hypogonadism (HH), a pathology characterized by delayed or absence of puberty. Binding of the guidance cue Slit2 to the receptor roundabout 3 (Robo3) has been proposed to modulate GnRH-1 cell motility and basal forebrain (bFB) access during migration. However, evidence suggests that Neural EGFL Like 2 (NELL2), not Slit2, binds to Robo3. To resolve this discrepancy, we analyzed GnRH-1 neuronal migration in NELL2, Robo3, and Slit2 knock-out mouse lines. Our data do not confirm a negative effect for monogenic Robo3 and Slit2 mutations on GnRH-1 neuronal migration from the nasal area to the brain. Moreover, we found no changes in GnRH-1 neuronal migration in the brain after NELL2 loss-of-function. However, we found that Slit2 loss-of-function alters the patterning of GnRH-1 cells in the brain, suggesting that Slit2 loss-of-function affects GnRH-1 cell positioning in the brain in a Robo3 independent fashion. Our results challenge previous theories on GnRH-1 neuronal migration mechanisms and provide a new impetus to identify and understand the complex genetic mechanisms causing disorders like Kallmann syndrome (KS) and HH. |
topic |
GnRH-1 olfactory bulbs Kallmann syndrome hypogonadotropic hypogonadism neuronal migration Robo |
url |
https://www.frontiersin.org/article/10.3389/fncel.2019.00070/full |
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