Other
13 Authors
- Wang Q,
- Li W,
- Hannan A,
- Wu Y,
- Ding Z,
- Anderson KE,
- Makrides N,
- Zhang X,
- Hawkins P,
- Lin CS,
- Peregrin J,
- Stephens L,
- Tao C
| First Author | Wang Q | Year | 2025 |
| Journal | Cell Rep | Volume | 44 |
| Issue | 8 | Pages | 116046 |
| PubMed ID | 40711883 | Mgi Jnum | J:371773 |
| Mgi Id | MGI:8242956 | Doi | 10.1016/j.celrep.2025.116046 |
| Citation | Wang Q, et al. (2025) FGF-induced phospholipase Cgamma signaling regulates lacrimal gland branching by competing with PI3K in phosphoinositide metabolism. Cell Rep 44(8):116046 |
| abstractText | Although the regulation of branching morphogenesis by spatially distributed cues is well established, the underlying intracellular signaling mechanisms are not well understood. The development of the lacrimal gland is driven by fibroblast growth factor (FGF) signaling, which activates phospholipase C gamma (PLCgamma). Here, we showed that mutating the PLCgamma1 binding site on Fgfr2 leads to ectopic branching and hyperplasia in the lacrimal gland, which was phenocopied by either deleting PLCgamma1 or disabling any of its SH2 domains. PLCgamma1 inactivation did not change the level of Fgfr2 or affect mitogen-activated protein kinase (MAPK) signaling but instead led to sustained AKT phosphorylation due to increased phosphatidylinositol 3,4,5-trisphosphate (PIP3) production. Consistent with this, the PLCgamma1 mutant phenotype can be reproduced by the elevation of phosphatidylinositol 3-kinase (PI3K) signaling in Pten knockout and attenuated by blocking AKT signaling. Our findings demonstrate that FGF-activated PLCgamma modulates PI3K signaling by shifting phosphoinositide metabolism, revealing the crucial role of PLCgamma in branching morphogenesis and organ size control. |
