FGF20-FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation in the organ of Corti.
Dev Dyn
; 250(2): 134-144, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-32735383
ABSTRACT
BACKGROUND:
Fibroblast Growth Factor 20 (FGF20)-FGF receptor 1 (FGFR1) signaling is essential for cochlear hair cell (HC) and supporting cell (SC) differentiation. In other organ systems, FGFR1 signals through several intracellular pathways including MAPK (ERK), PI3K, phospholipase C ɣ (PLCɣ), and p38. Previous studies implicated MAPK and PI3K pathways in HC and SC development. We hypothesized that one or both would be important downstream mediators of FGF20-FGFR1 signaling for HC differentiation.RESULTS:
By inhibiting pathways downstream of FGFR1 in cochlea explant cultures, we established that both MAPK and PI3K pathways are required for HC differentiation while PLCÉ£ and p38 pathways are not. Examining the canonical PI3K pathway, we found that while AKT is necessary for HC differentiation, it is not sufficient to rescue the Fgf20-/- phenotype. To determine whether PI3K functions downstream of FGF20, we inhibited Phosphatase and Tensin Homolog (PTEN) in Fgf20-/- explants. Overactivation of PI3K resulted in a partial rescue of the Fgf20-/- phenotype, demonstrating a requirement for PI3K downstream of FGF20. Consistent with a requirement for the MAPK pathway for FGF20-regulated HC differentiation, we show that treating Fgf20-/- explants with FGF9 increased levels of dpERK.CONCLUSIONS:
Together, these data provide evidence that both MAPK and PI3K are important downstream mediators of FGF20-FGFR1 signaling during HC and SC differentiation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organ of Corti
/
Cell Differentiation
/
MAP Kinase Signaling System
/
Receptor, Fibroblast Growth Factor, Type 1
/
Fibroblast Growth Factors
Limits:
Animals
Language:
En
Journal:
Dev Dyn
Journal subject:
ANATOMIA
Year:
2021
Document type:
Article
Affiliation country:
United States