Fig. 7
From: Notch transactivates Rheb to maintain the multipotency of TSC-null cells
Spontaneous renal tumorigenesis induced by cell-type-specific loss of Tsc1. a H&Es of Tsc1 f/f (control) kidney, n = 3. b Kidney lesions in Nestin-TamCre;Tsc1 f/f; c H&Es of Nestin-TamCre;Tsc1 f/f kidneys, n = 3: (i) cysts; (ii) RIN (arrow); (iii) papillary carcinoma (micro-invasion-arrow); (iv) invasive papillary renal cell carcinoma (dashed line indicates border between RCC and normal kidney). Tamoxifen was injected intraperitoneally into 2–3-month-old mice at the dose of 120 mg/kg/day for two consecutive days. Mice were harvested at the age of 7 months. d–f Expression of nestin (red) in renal spindle-shape tumor cells. Expression of phospho-S6 within renal lesions (green). g Co-expression of nestin and phospho-S6 in spindle-shape tumor cells (arrowheads). h Expression of Cre recombinase within renal lesions of Nestin-TamCre;Tsc1 f/f mice. i The role of the Rheb-Notch-Rheb loop during NSC maintenance. The loss of Tsc1 blocks the differentiation of NSCs and progenitors via activation of the Rheb-Notch-Rheb loop, which leads to the amplified oscillation of HES1 and RHEB, controlled by the fluctuation in the binding of N1ICD to their activating NREs
