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Altered cholesterol biosynthesis causes precocious neurogenesis in the developing mouse forebrain
- Source :
- Neurobiology of Disease, Vol 91, Iss, Pp 69-82 (2016)
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- We previously reported a mutation in the cholesterol biosynthesis gene, hydroxysteroid (17-beta) dehydrogenase 7 (Hsd17b7(rudolph)), that results in striking embryonic forebrain dysgenesis. Here we describe abnormal patterns of neuroprogenitor proliferation in the mutant forebrain, namely, a decrease in mitotic cells within the ventricular zone (VZ) and an increase through the remainder of the cortex by E11.5. Further evidence suggests mutant cells undergo abnormal interkinetic nuclear migration (IKNM). Furthermore, intermediate progenitors are increased at the expense of apical progenitors by E12.5, and post-mitotic neurons are expanded by E14.5. In vitro primary neuron culture further supports our model of accelerated cortical differentiation in the mutant. Combined administration of a statin and dietary cholesterol in utero achieved partial reversal of multiple developmental abnormalities in the Hsd17b7(rudolph) embryo, including the forebrain. These results suggest that abnormally increased levels of specific cholesterol precursors in the Hsd17b7(rudolph) embryo cause cortical dysgenesis by altering patterns of neurogenesis.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Interkinetic nuclear migration
Cortical neurogenesis
Neurogenesis
Cellular differentiation
Mice, Transgenic
Nerve Tissue Proteins
Cell fate determination
Biology
Article
lcsh:RC321-571
03 medical and health sciences
Dysgenesis
Prosencephalon
0302 clinical medicine
Internal medicine
medicine
Animals
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Cell Proliferation
Neurons
Cell Differentiation
Embryo
Embryo, Mammalian
Neural progenitors
Cholesterol
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Cell fate
Neurology
Forebrain
Cholesterol biosynthesis
Neuron
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 09699961
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Disease
- Accession number :
- edsair.doi.dedup.....103df5a7fc0bd6c692f33f565bf44e47