Fig. 8
From: Notch ankyrin domain: evolutionary rise of a thermodynamic sensor
Heat flux links mitochondrial activity to differentiation of the host cell. a Immunohistochemical visualisation of intracellular Notch-1, β-catenin, and MCM1 in neural progenitor cells at 35 °C and 39 °C (ROS: H2O2) (Control micrographs: Additional file 1: Fig. S3). Scale bars (from top to bottom in µm): [5, 10, 20, 35]. b The top box plots show expression of Notch-1 downstream mediators after incubation of cells for 2 h at 35 °C (t1) and 39 °C (t2) in growth medium (GM). The bottom box plots show expression of pro-neural transcription factors after incubation of cells for 2 h at 35 °C (t1) and 39 °C (t2) in neural induction medium (NIM) (*p < 0.01). The schematic diagram (bottom right) shows topology of an “AND logic” gate that operates by input from mitochondrial ROS/GTP and heat flux to regulate the tempo of differentiation. c Expression of pro-neural transcription factors after RNAi-mediated depletion of notch-1 mRNA, incubation of 16 h in growth medium, and induction of differentiation by incubation in neural induction medium for 2 h at 35 °C (t1) and 39 °C (t2) (*p < 0.01). d Schematic image shows the proposed role of Notch-1 ankyrin as a thermodynamic sensor whereby Notch-1 pathway amplifies mitochondrial activity and the resultant thermal energy functions as negative feedback to recalibrate the activity of the signalling cascade. During cannibalisation of erythroblasts, access to copious heme and mitochondrial hyperactivation usurps this mechanism to supress Notch-1 and trigger accelerated differentiation of neural progenitor cells