Figure 7
Schematic representation of the proposed TCS pathogenesis model. (a) Tcof1 haploinsufficiency leads to deficient rRNA synthesis and processing and consequent nucleolar stress. Nucleolar disruption results in: (i) stabilization of Tp53 and upregulation of pro-apoptotic genes; and (ii) an increase of cellular ROS, with the resultant upregulation of stress-response genes and decreased abundance of Cnbp. In addition to its role in ribosome biogenesis, Treacle may also be required in DNA damage repair response for protection of the neuroepithelium from oxidative stress-induced cell death. These events lead to an increase of cell death and decrease of cell proliferation, which result in facial abnormalities. Shaded in grey: ROS and Cnbp in TCS pathogenesis. (b) Proposed mechanism for craniofacial defects rescued by Cnbp. Overexpression of cnbp in TCS-like fish prevents the redox-responsive genes’ upregulation and leads to decrease of cell death and craniofacial malformations
