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Yin Yang 1 is critical for mid-hindbrain neuroepithelium development and involved in cerebellar agenesis.
- Source :
-
Molecular brain [Mol Brain] 2020 Jul 23; Vol. 13 (1), pp. 104. Date of Electronic Publication: 2020 Jul 23. - Publication Year :
- 2020
-
Abstract
- The highly conserved and ubiquitously expressed transcription factor Yin Yang 1 (Yy1), was named after its dual functions of both activating and repressing gene transcription. Yy1 plays complex roles in various fundamental biological processes such as the cell cycle progression, cell proliferation, survival, and differentiation. Patients with dominant Yy1 mutations suffer from central nervous system (CNS) developmental defects. However, the role of Yy1 in mammalian CNS development remains to be fully elucidated. The isthmus organizer locates to the mid-hindbrain (MHB) boundary region and serves as the critical signaling center during midbrain and cerebellar early patterning. To study the function of Yy1 in mesencephalon/ rhombomere 1 (mes/r1) neuroepithelium development, we utilized the tissue-specific Cre-LoxP system and generated a conditional knockout mouse line to inactivate Yy1 in the MHB region. Mice with Yy1 deletion in the mes/r1 region displayed cerebellar agenesis and dorsal midbrain hypoplasia. The Yy1 deleted neuroepithelial cells underwent cell cycle arrest and apoptosis, with the concurrent changes of cell cycle regulatory genes expression, as well as activation of the p53 pathway. Moreover, we found that Yy1 is involved in the transcriptional activation of Wnt1 in neural stem cells. Thus, our work demonstrates the involvement of Yy1 in cerebellar agenesis and the critical function of Yy1 in mouse early MHB neuroepithelium maintenance and development.
- Subjects :
- Animals
Apoptosis
Cell Cycle
Cell Polarity
Cell Proliferation
Cerebellum pathology
Mice, Knockout
Mutation genetics
Promoter Regions, Genetic genetics
Rhombencephalon pathology
Tumor Suppressor Protein p53 metabolism
Wnt1 Protein genetics
Wnt1 Protein metabolism
Cerebellum abnormalities
Cerebellum metabolism
Neuroepithelial Cells metabolism
Rhombencephalon metabolism
YY1 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1756-6606
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular brain
- Publication Type :
- Academic Journal
- Accession number :
- 32703236
- Full Text :
- https://doi.org/10.1186/s13041-020-00643-z