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.
Highlights
Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor which exerts multiple functions in various cellular events by activating or repressing gene transcription, modifying DNA conformation and controlling protein activity [1,2,3,4]
Due to the existence of non-neuroepithelial cells (NECs) tissue, a background level of Yin Yang 1 (Yy1) mRNA and protein could still be detected by these two methods, but we observed a persistent reduction of Yy1 expression at E9.5 and E10.5 (Supplementary Figure S1A&B, Fig. 3e; For E10.5 qPCR, mutant 2-ΔΔCq = 0.399 ± 0.026)
YY1 protein was completely undetectable in the midhindbrain neural tube of the En1Cre/+; Yy1flox/flox mutant mice, but was still expressed in the meninges throughout the mes/r1 region and in the roof plate cells that will develop into the 4th ventricle choroid plexus
Summary
Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor which exerts multiple functions in various cellular events by activating or repressing gene transcription, modifying DNA conformation and controlling protein activity [1,2,3,4]. Numerous studies have suggested that YY1 regulates the activity of promoters and enhancers of genes that are implicated in the cell cycle, cell apoptosis, and cancer progression [3, 5]. Dong and Kwan Molecular Brain (2020) 13:104 function of Yy1 in oligodendrocyte differentiation has been reported through a conditional knockout mouse model [10]. A group of researchers uncovered that Yy1 exerts a stage-dependent role by regulating metabolic pathways and protein synthesis during cerebral corticogenesis. In the mouse forebrain cortical neural progenitor cells (NPCs), Yy1 controls cell proliferation and survival [11]. The mechanism leading to neural developmental defects in other brain regions is still unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
