Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.

The organizational action of testosterone during critical periods of development is the cause of numer o ussex differences in the brain. However, sex differences in neuritogenesis have been detectedin primary neuronal hypothalamic cultures prepared before the peak of testosterone production by fetal...

Full description

Bibliographic Details
Main Authors: Scerbo, M.J., Freire-Regatillo, A., Cisternas, C.D., Brunotto, M., Arévalo, M.A., Garcia-Segura, L.M., Cambiasso, M.J.
Format: publishedVersion
Language:eng
Published: Frontiers in Cellular Neuroscience. 2017
Subjects:
Online Access:http://hdl.handle.net/11086/4896
_version_ 1801213646705000448
author Scerbo, M.J.
Freire-Regatillo, A.
Cisternas, C.D.
Brunotto, M.
Arévalo, M.A.
Garcia-Segura, L.M.
Cambiasso, M.J.
author_facet Scerbo, M.J.
Freire-Regatillo, A.
Cisternas, C.D.
Brunotto, M.
Arévalo, M.A.
Garcia-Segura, L.M.
Cambiasso, M.J.
author_sort Scerbo, M.J.
collection Repositorio Digital Universitario
description The organizational action of testosterone during critical periods of development is the cause of numer o ussex differences in the brain. However, sex differences in neuritogenesis have been detectedin primary neuronal hypothalamic cultures prepared before the peak of testosterone production by fetal testis. In the present study we assessed the hypothesis of that cell-autonomous action of sex chromosomes can differentially regulate the expression of the neuritogenic gene neurogenin 3 (Ngn3) in male and female hypothalamic neurons, generating sex differences in neuronal development. Neuronal cultures were prepared from male and female E14 mouse hypothalami, before the fetal peak of testosterone. Female neurons showed enhanced neuritogenesis and higher expressionof Ngn3 than maleneurons. The silencing of Ngn3 abolished sex differences in neuritogenesis, decreasing the differentiation off e mal e neurons. The sex difference in Ngn3 expression was determined by sex chromosomes, as demonstrated using the four core genotypes mouse model, in which a spontaneous deletion of the testis-determining gene Sry from the Y chromosome was combined with the insertion of the Sry gene onto an autosome. In addition, the expression of Ngn3, which is also known to mediate the neuritogenic actions of estradiol, was increased in the cultures treated with the hormone, but only in those from male embryos. Furthermore, the hormone reversed the sex difference sin neuritogenesis promoting the differentiation of male neurons. These findings indicate that Ngn3 mediates both cell-autonomous actions of sex chromosomes and hormonal effects on neuritogenesis.
format publishedVersion
id rdu-unc.4896
institution Universidad Nacional de Cordoba
language eng
publishDate 2017
publisher Frontiers in Cellular Neuroscience.
record_format dspace
spelling rdu-unc.48962022-06-08T11:39:07Z Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development. Scerbo, M.J. Freire-Regatillo, A. Cisternas, C.D. Brunotto, M. Arévalo, M.A. Garcia-Segura, L.M. Cambiasso, M.J. Sex characteristics Sex chromosomes Estradiol Neuritogenesis Hypothalamic neurons publishedVersion The organizational action of testosterone during critical periods of development is the cause of numer o ussex differences in the brain. However, sex differences in neuritogenesis have been detectedin primary neuronal hypothalamic cultures prepared before the peak of testosterone production by fetal testis. In the present study we assessed the hypothesis of that cell-autonomous action of sex chromosomes can differentially regulate the expression of the neuritogenic gene neurogenin 3 (Ngn3) in male and female hypothalamic neurons, generating sex differences in neuronal development. Neuronal cultures were prepared from male and female E14 mouse hypothalami, before the fetal peak of testosterone. Female neurons showed enhanced neuritogenesis and higher expressionof Ngn3 than maleneurons. The silencing of Ngn3 abolished sex differences in neuritogenesis, decreasing the differentiation off e mal e neurons. The sex difference in Ngn3 expression was determined by sex chromosomes, as demonstrated using the four core genotypes mouse model, in which a spontaneous deletion of the testis-determining gene Sry from the Y chromosome was combined with the insertion of the Sry gene onto an autosome. In addition, the expression of Ngn3, which is also known to mediate the neuritogenic actions of estradiol, was increased in the cultures treated with the hormone, but only in those from male embryos. Furthermore, the hormone reversed the sex difference sin neuritogenesis promoting the differentiation of male neurons. These findings indicate that Ngn3 mediates both cell-autonomous actions of sex chromosomes and hormonal effects on neuritogenesis. publishedVersion 2017-08-07T17:07:51Z 2017-08-07T17:07:51Z 2014 article Scerbo , M.J, Freire-regatillo, A, Cisternas , C.D, Brunotto, M, Arevalo, L.M, Cambiasso, MJ. Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development. Front Cell Neurosci. 2014;8(8): 1-13. 1662-5102 http://hdl.handle.net/11086/4896 eng Atribución-NoComercial-CompartirIgual 4.0 Internacional https://creativecommons.org/licenses/by-nc-sa/4.0/deed.es Frontiers in Cellular Neuroscience.
spellingShingle Sex characteristics
Sex chromosomes
Estradiol
Neuritogenesis
Hypothalamic neurons
Scerbo, M.J.
Freire-Regatillo, A.
Cisternas, C.D.
Brunotto, M.
Arévalo, M.A.
Garcia-Segura, L.M.
Cambiasso, M.J.
Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.
title Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.
title_full Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.
title_fullStr Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.
title_full_unstemmed Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.
title_short Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.
title_sort neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development
topic Sex characteristics
Sex chromosomes
Estradiol
Neuritogenesis
Hypothalamic neurons
url http://hdl.handle.net/11086/4896
work_keys_str_mv AT scerbomj neurogenin3mediatessexchromosomeeffectsonthegenerationofsexdifferencesinhypothalamicneuronaldevelopment
AT freireregatilloa neurogenin3mediatessexchromosomeeffectsonthegenerationofsexdifferencesinhypothalamicneuronaldevelopment
AT cisternascd neurogenin3mediatessexchromosomeeffectsonthegenerationofsexdifferencesinhypothalamicneuronaldevelopment
AT brunottom neurogenin3mediatessexchromosomeeffectsonthegenerationofsexdifferencesinhypothalamicneuronaldevelopment
AT arevaloma neurogenin3mediatessexchromosomeeffectsonthegenerationofsexdifferencesinhypothalamicneuronaldevelopment
AT garciaseguralm neurogenin3mediatessexchromosomeeffectsonthegenerationofsexdifferencesinhypothalamicneuronaldevelopment
AT cambiassomj neurogenin3mediatessexchromosomeeffectsonthegenerationofsexdifferencesinhypothalamicneuronaldevelopment