Regulation of neuronal diversity in the Xenopus retina by Delta signalling

Abstract

To generate the variety of mature neurons and glia found in the developing retina, the competence of pluripotent progenitor cells to respond to extracellular signals must be controlled. Delta, a ligand of the Notch receptor, is a candidate for regulating progenitor competence on the grounds that activation of the pathway involving Notch and Delta can inhibit cellular differentiation. Here we test this possibility in the developing Xenopus retina by misexpression of Delta messenger RNA. We find that Delta-misexpressing cells with wild-type neighbours adopt earlier fates, primarily becoming ganglion cells and cone photoreceptors. Progenitors transfected with Delta later in development also produce rod photoreceptors, but not the latest-generated cell types, demonstrating the importance of timing in Delta function. We conclude that Delta signalling in the vertebrate retina is a basic regulatory mechanism that can be used to generate neuronal diversity.

Thyroid hormone promotes neurogenesis in the Xenopus spinal cord

“…X-Delta-1 expression in this ventricular layer, which harbors many proliferating cells (Thors et al, 1982b), is strongly up-regulated. Therefore, Delta-Notch signalling may take place between proliferating cells similar to the Xenopus retina (Dorsky et al, 1995(Dorsky et al, , 1997 and may continue to influence neuronal cell fate decisions possibly by mediating lateral inhibition between neighboring cells. Simultaneously, the expression domains of XNeuroD and XMyT1 expand in a region lateral to the ventricular zone, similar to NeuroD expression in the mammalian spinal cord (Lee et al, 1995;Ma et al, 1996), suggesting that neurons are determined and begin to differentiate while they are displaced laterally from the ventricular zone.…”

Molecular Control of Retinal Ganglion Cell Specification and Differentiation

“…Besides these diffusible signals, Dll-Notch signaling mediated by cell-cell contacts also limits RGC production. Constitutively activated Notch and elevated Dll signal are shown to decrease RGC generation whereas inhibiting Notch signaling has the opposite effect (Ahmad et al, 1997;Austin et al, 1995;Dorsky et al, 1997;Dorsky et al, 1995;Nelson et al, 2007). Interestingly, both Shh and VEGF signaling activates expression of the DllNotch effector gene Hes1, which has an activity to suppress RGC differentiation (Hashimoto et al, 2006;Sakagami et al, 2009;Wang et al, 2005).…”

Becoming glial in the neural retina

“…Conversely, Notch may play a more permissive role in determining glial fates in the amphibian retina. Dorsky et al(1997) tested the effects of expressing high levels of Delta STU , a truncated Notch ligand (Chitnis et al, 1995) that interferes with activation of the Notch pathway in retinal progenitors. Cells misexpressing Delta STU never differentiated as Mü ller glia, but adopted earlier neuronal fates .…”