Pubertal development is impaired in mice lacking the basic helix-loop-helix transcription factor Nhlh2. The mechanisms underlying changes in reproduction in Nhlh2-deficient mice (Nhlh2(-/-)) are unclear. Here we show that hypothalamic GnRH-1 content is reduced in adult Nhlh2(-/-) mice as is the number of GnRH-1 neurons localized to mid- and caudal hypothalamic regions. This reduction was detected postnatally after normal migration of GnRH-1 neurons within nasal regions had occurred. Phenotype rescue experiments showed that female Nhlh2(-/-) mice were responsive to estrogen treatment. In contrast, puberty could not be primed in female Nhlh2(-/-) mice with a GnRH-1 regimen. The adenohypophysis of Nhlh2(-/-) mice was hypoplastic although it contained a full complement of the five anterior pituitary cell types. GnRH-1 receptors (GnRHRs) were reduced in Nhlh2(-/-) pituitary gonadotropes as compared with wild type. In vitro assays indicated that Nhlh2 expression is regulated in parallel with GnRHR expression. However, direct transcriptional activity of Nhlh2 on the GnRHR promoter was not found. These results indicate that Nhlh2 plays a role in the development and functional maintenance of the hypothalamic-pituitary-gonadal axis at least at two levels: 1) in the hypothalamus by regulating the number and distribution of GnRH-1 neurons and, 2) in the developing and mature adenohypophysis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1210/me.2005-0337 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A global gene regulatory program and its region-specific regulator partition neurons into commissural and ipsilateral projection types.
Sci Adv
May 2024
National Institute of Genetics, Graduate University for Advanced Studies, Sokendai, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
Article Synopsis
- Understanding how genetic programs influence neuron classification is crucial for nervous system development, with neurons categorized into commissural (crossing midline) and ipsilateral (not crossing) types.
- We identified transcription factors Nhlh1 and Nhlh2 as key regulators controlling laterality in commissural axons in mice, mediating the expression of Robo3, a guidance molecule.
- Additionally, Isl1, found in ipsilateral neurons, inhibits Robo3 induction by Nhlh1/2, highlighting a complex interplay between global mechanisms and specific neuron regulators in determining axon paths.
Transcriptional profiling of Kiss1 neurons from arcuate and rostral periventricular hypothalamic regions in female mice.
Reproduction
January 2024
Department of Physiology, Development and Neuroscience, Reproductive Physiology Group, Physiology Building, Downing Street, University of Cambridge, Cambridge, UK.
In Brief: The transcriptional profiles of Kiss1 neurons from the arcuate and the rostral periventricular region of the third ventricle of the hypothalamus have been directly compared in diestrous female mice. Differentially expressed genes provide molecular signatures for these two populations of Kiss1 neurons and insights into their physiology.
Abstract: The neuropeptide kisspeptin is produced by Kiss1 neurons and is required for normal mammalian fertility.
In Silico Examination of Single Nucleotide Missense Mutations in , a Gene Linked to Infertility and Obesity.
Int J Mol Sci
February 2023
Department of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA 24060, USA.
Continual advances in our understanding of the human genome have led to exponential increases in known single nucleotide variants. The characterization of each of the variants lags behind. For researchers needing to study a single gene, or multiple genes in a pathway, there must be ways to narrow down pathogenic variants from those that are silent or pose less pathogenicity.
View Article and Find Full Text PDFReference Genes across Nine Brain Areas of Wild Type and Prader-Willi Syndrome Mice: Assessing Differences in , , and Expression.
Int J Mol Sci
August 2022
Medical Faculty, Core Facility Transgenic Animal and Genetic Engineering Models (TRAM), University of Muenster, Von-Esmarch-Str. 56, 48149 Muenster, Germany.
Prader−Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by the deletion or inactivation of paternally expressed imprinted genes at the chromosomal region 15q11−q13. The PWS-critical region (PWScr) harbors tandemly repeated non-protein coding IPW-A exons hosting the intronic SNORD116 snoRNA gene array that is predominantly expressed in brain. Paternal deletion of PWScr is associated with key PWS symptoms in humans and growth retardation in mice (PWScr model).
View Article and Find Full Text PDFDietary Conjugated Linoleic Acid Reduces Body Weight and Fat in and Mouse Models of Prader-Willi Syndrome.
Nutrients
February 2022
Department of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA 24060, USA.
Prader-Willi Syndrome (PWS) is a human genetic condition that affects up to 1 in 10,000 live births. Affected infants present with hypotonia and developmental delay. Hyperphagia and increasing body weight follow unless drastic calorie restriction is initiated.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!