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Postnatal development of the wild-type and weaver cerebellum after embryonic administration of propylthiouracil (PTU)
1Department of Neurosciences, Roche Institute of Molecular Biology, Nutley, NJ.
Abstract:
In this study we used propylthiouracil (PTU), a thyroid hormone-inhibiting compound, to render +/+, wv/+, and wv/wv embryos hypothyroid in order to test if the appearance of external granule layer (EGL) cell death in the weaver cerebellum is affected by alteration of granule cell development. At birth, the number of EGL cells in the PTU-treated cerebellum was reduced, compared to control animals, by 50%. Also, the amount of cell death was reduced in the PTU-treated wv/wv cerebellum. As adults, no differences were seen between PTU-treated and untreated mutant or normal cerebella. If the hypothyroid treatment that results in a 50% decrease in EGL cell number is due to an extension of cell cycling time, then the expression of the weaver phenotype of cell death likely follows granule cell exit from the cell cycle.
Insights
Propylthiouracil (PTU) treatment reduced external granule layer (EGL) cell numbers and cell death in weaver cerebella. This suggests weaver-associated cell death occurs after granule cells exit the cell cycle.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- The weaver (wv) mouse mutation causes cerebellar abnormalities, including external granule layer (EGL) cell death.
- Granule cell development is crucial for cerebellar formation and function.
- Thyroid hormones play a role in cerebellar development.
Purpose of the Study:
- To investigate the impact of hypothyroidism on EGL cell death in weaver mutant mice.
- To determine if altering granule cell development affects the weaver phenotype.
Main Methods:
- Hypothyroidism was induced in mouse embryos (+/+, wv/+, and wv/wv) using propylthiouracil (PTU).
- EGL cell numbers and cell death were quantified at birth.
- Cerebella were analyzed in both young and adult animals.
Main Results:
- PTU treatment reduced EGL cell numbers by 50% in all genotypes at birth.
- PTU treatment decreased the amount of cell death in the EGL of wv/wv cerebella.
- No significant differences in cerebellar structure were observed between PTU-treated and untreated animals as adults.
Conclusions:
- The weaver phenotype of EGL cell death appears to be dependent on granule cell exit from the cell cycle.
- Hypothyroidism, induced by PTU, affects early granule cell development but not the adult weaver phenotype.
- These findings provide insights into the developmental mechanisms underlying cerebellar mutations.