Notch-Delta signaling is required for spatial patterning and Muller glia differentiation in the zebrafish retina

Notch-Delta signaling has been implicated in several alternative modes of function in the vertebrate retina. To further investigate these functions. we examined retinas from zebrafish embryos in which bidirectional Notch-Delta signaling was inactivated either by the mind bomb (nub) mutation, which disrupts E3 ubiquitin ligase activity, or by treatment with gamma-secretase inhibitors, which prevent intramembrane proteolysis of Notch and Delta. We found that inactivating Notch-Delta signaling did not prevent differentiation of retinal neurons, but it did disrupt spatial patterning in both the apical-basal and planar dimensions of the retinal epithelium. Retinal neurons differentiated, but their laminar arrangement was disrupted. Photoreceptor differentiation was initiated normally, but its progression was slowed. Although confined to the apical retinal surface as in normal retinas, the planar organization of cone photoreceptors was disrupted: cones of the same spectral subtype were clumped rather than regularly spaced. In contrast to neurons, Muller glia failed to differentiate suggesting an instructive role for Notch-Delta signaling in gliogenesis. (C) 2004 Elsevier Inc. All rights reserved.