Functional study of Yin Yang 1 in mouse mid-hindbrain development
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AbstractThe multifunctional transcription factor Yin Yang 1 (YY1) was named after its dual roles of both activating and repressing gene transcription. YY1 has complex functions in various fundamental biological processes such as cell survival, proliferation, and differentiation, thus affecting embryogenesis. Mouse embryos encounter peri-implantation lethality when Yy1 was completely inactivated. Ablation of Yy1 in Xenopus embryos indicates it is essential for neural induction and patterning. Knockdown YY1a in zebrafish embryos suggests its function in early brain development as well. Numbers of works have revealed the necessity of Yy1 for stem cell development in different tissues with various mechanisms. However, the role of Yy1 in mammalian central nervous system (CNS) development remains to be elucidated.
As a well-characterized system to study the development of CNS, the mid-hindbrain boundary (MHB) isthmus organizer controls the proper regionalization of mesen-metencephalon, then specify cerebellar stem cells from the ventricular zone and rhombic lip giving rise to the GABAergic and glutamatergic neurons respectively. Disruption of these processes may cause brain structure malformation and severe CNS disorders. Yy1 is ubiquitously expressed in the developing cerebellum.
By employing the tissue-specific Cre-LoxP system, we obtained MHB Yy1 conditional knockout mice. The mutant mice displayed cerebellar agenesis and truncated midbrain despite the normal development of the other brain regions. Upon Cre expression, the MHB tissue gradually disintegrated during development. Yy1 inactivation in the neuroepithelial cells resulted in significant cell apoptosis, cell cycle arrest and aberrant cell specification. The expression level of a group of cell cycle regulators also changed in Yy1 deleted MHB cells. Together our data indicate the crucial role of Yy1 in neuroepithelial cells proliferation, survival and in early brain region patterning.
All Author(s) ListDONG Xiao Nan, KWAN Kin Ming
Name of ConferenceTokyo 2018 Cell and Developmental Biology Meeting
Start Date of Conference05/06/2018
End Date of Conference08/06/2018
Place of ConferenceTokyo
Country/Region of ConferenceJapan
LanguagesEnglish-United States

Last updated on 2018-25-10 at 15:10