ArticleHuman molecular genetics2015
Analysis of hedgehog signaling in cerebellar granule cell precursors in a conditional Nsdhl allele demonstrates an essential role for cholesterol in postnatal CNS development.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Cellular mechanisms of brain lipid metabolism in health and disease.Nature cell biology · 2026Review
- Prenatal MRI features of fetal complete agenesis of the corpus callosum associated with unilateral hemispheric cortical malformation: a retrospective study.Frontiers in radiology · 2026Article
- Emerging Functional Connections Between Metabolism and Epigenetic Remodeling in Neural Differentiation.Molecular neurobiology · 2024Review
- Article
- Lipid Rafts: The Maestros of Normal Brain Development.Biomolecules · 2024Review
- The Cerebellum in Niemann-Pick C1 Disease: Mouse Versus Man.Cerebellum (London, England) · 2023Review
- Mass Spectrometry-Based Analysis of Lipid Involvement in Alzheimer's Disease Pathology-A Review.Metabolites · 2022Review
- ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.iScience · 2021Article
- Article
- Cholesterol Pathway Inhibition Induces TGF-β Signaling to Promote Basal Differentiation in Pancreatic Cancer.Cancer cell · 2020Article
- Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea.Cellular and molecular life sciences : CMLS · 2020Article
- NPC1 Deficiency in Mice is Associated with Fetal Growth Restriction, Neonatal Lethality and Abnormal Lung Pathology.Journal of clinical medicine · 2019Article
- Metabolism and Biological Activities of 4-Methyl-Sterols.Molecules (Basel, Switzerland) · 2019Review
- Role of cholesterol and sphingolipids in brain development and neurological diseases.Lipids in health and disease · 2019Review
- NSDHL-containing duplication at Xq28 in a male patient with autism spectrum disorder: a case report.BMC medical genetics · 2018Article
- MARVELD1 depletion leads to dysfunction of motor and cognition via regulating glia-dependent neuronal migration during brain development.Cell death & disease · 2018Article
- Multiple ligand binding sites regulate the Hedgehog signal transducer Smoothened in vertebrates.Current opinion in cell biology · 2018Review
- Statins Synergize with Hedgehog Pathway Inhibitors for Treatment of Medulloblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Intrauterine Reprogramming of the Polycystic Ovary Syndrome: Evidence from a Pilot Study of Cord Blood Global Methylation Analysis.Frontiers in endocrinology · 2017Article
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7 authors at 2 institutions in 1 country.
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Abstract
NSDHL is a 3β-hydroxysterol dehydrogenase that is involved in the removal of two C-4 methyl groups in one of the later steps of cholesterol biosynthesis. Mutations in the gene encoding the enzyme are responsible for the X-linked, male lethal mouse mutations bare patches and striated, as well as most cases of human CHILD syndrome. Rare, hypomorphic NSDHL mutations are also associated with X-linked intellectual disability in males with CK syndrome. Since hemizygous male mice with Nsdhl mutations die by midgestation, we generated a conditional targeted Nsdhl mutation (Nsdhl(tm1.1Hrm)) to investigate the essential role of cholesterol in the early postnatal CNS. Ablation of Nsdhl in radial glia using GFAP-cre resulted in live-born, normal appearing affected male pups. However, the pups develop overt ataxia by postnatal day 8-10 and die shortly thereafter. Histological abnormalities include progressive loss of cortical and hippocampal neurons, as well as deficits in the proliferation and migration of cerebellar granule precursors and subsequent massive apoptosis of the cerebellar cortex. We replicated the granule cell precursor proliferation defect in vitro and demonstrate that it results from defective signaling by SHH. Furthermore, this defect is almost completely rescued by supplementation of the culture media with exogenous cholesterol, while methylsterol accumulation above the enzymatic block appears to be associated with increased cell death. These data support the absolute requirement for cholesterol synthesis in situ once the blood-brain-barrier forms and cholesterol transport to the fetus is abolished. They further emphasize the complex ramifications of cholesterogenic enzyme deficiency on cellular metabolism.
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