Fig. 6: FGF signaling activates mTOR-dependent autophagy in MSCs.
From: Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis
a–i mTOR-dependent autophagy is downregulated in Gli1CreER;Fgfr1fl/fl mice. a Hierarchical clustering of control and Gli1CreER;Fgfr1fl/fl mice. b Volcano plot showing 2019 upregulated genes and 1447 downregulated genes. c Significant signaling pathways analyzed with Ingenuity Pathway Analysis (IPA). d Expression of FGFR1, LC3 and p-ULK1 in mesenchyme of incisors from control and Gli1CreER;Fgfr1fl/fl mice. e–h Expression of autophagy substrate P62 in control and Gli1CreER;Fgfr1fl/fl mice. i Expression of p-mTOR and its downstream effectors p-P70S6K and pS6 in control and mutant mice. j–p FGF/p-JNK signaling regulates mTOR-dependent autophagy activation in MSCs. j Western blot of p-AKT, AKT, p-P38, P38, p-ERK, ERK, p-JNK, and JNK in proximal mesenchyme from control and mutant mice. k and l Expression of p-JNK and β-gal in the proximal mesenchyme of incisors from Gli1-LacZ mice. m–p Expression of p-JNK in control and Gli1CreER;Fgfr1fl/fl mice. q Relative protein level in (d). FGFR1/β-Actin: P = 0.0001; LC3II/LC3I: P = 0.0006; p-ULK1/β-Actin: P < 0.0001. r Relative protein level in (i). p-mTOR/mTOR: P = 0.0056; p-P70S6K/P70S6K: P = 0.0016; pS6/S6: P = 0.0001. s Relative protein level in (j). p-Akt/Akt: P = 0.3485; p-P38/P38: P = 0.9988; p-ERK/ERK: P = 0.0025; p-JNK/JNK: P < 0.0001. t Relative fluorescent intensity of P62 and p-JNK. P62: P < 0.0001; p-JNK: P = 0.0019. For q–t, n = 3 and each data point represent one biological replicate, with unpaired Student’s t-test performed. All data are expressed as the mean ± SD. Source data are provided as a Source Data file. **P < 0.01, ***P < 0.001, ****P < 0.0001. Each experiment was repeated independently three times. White dotted line outlines the cervical loop. Scale bars, 100 μm.
