Opposing Actions of Fgf8a on Notch Signaling Distinguish Two Muller Glial Cell Populations that Contribute to Retina Growth and Regeneration

Abstract

The teleost retina grows throughout life and exhibits a robust regenerative response following injury. Critical to both these events are Muller glia (or, Muller glial cells; MGs), which produce progenitors for retinal growth and repair. We report that Fgf8a may be an MG niche factor that acts through Notch signaling to regulate spontaneous and injury-dependent MG proliferation. Remarkably, forced Fgf8a expression inhibits Notch signaling and stimulates MG proliferation in young tissue but increases Notch signaling and suppresses MG proliferation in older tissue. Furthermore, cessation of Fgf8a signaling enhances MG proliferation in both young and old retinal tissue. Our study suggests that multiple MG populations contribute to retinal growth and regeneration, and it reveals a previously unappreciated role for Fgf8a and Notch signaling in regulating MG quiescence, activation, and proliferation.