Involvement of Atm and Trp53 in neural cell loss due to Terf2 inactivation during mouse brain development.
Jusik KimInseo ChoiYoungsoo LeePublished in: Histochemistry and cell biology (2017)
Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure. This neural loss was rescued partially in both Atm and Trp53 deficiency, but not in an Atr-deficient background in the mouse. Atm inactivation resulted in incomplete brain structures, whereas p53 deficiency led to the formation of multinucleated giant neural cells and the disruption of the brain structure. These giant neural cells disappeared in Lig4 deficiency. These data demonstrate ATM and TP53 are important for the maintenance of telomere homeostasis and the surveillance of telomere dysfunction during neurogenesis.
Keyphrases
- induced apoptosis
- dna damage
- oxidative stress
- dna damage response
- endoplasmic reticulum stress
- dna repair
- signaling pathway
- cell cycle arrest
- cerebral ischemia
- resting state
- public health
- white matter
- stem cells
- subarachnoid hemorrhage
- multiple sclerosis
- high resolution
- cell death
- replacement therapy
- gene expression
- machine learning
- functional connectivity
- mesenchymal stem cells
- bone marrow
- mass spectrometry