Abstract
BackgroundDuring visual system development, multiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum. This information is required for the topographic mapping of retinal ganglion cell axons on the tectum. Meis1 is a TALE-class homeodomain transcription factor known to specify anterior-posterior identity in the hindbrain, but its role in visual system patterning has not been investigated.Resultsmeis1 is expressed in both the presumptive retina and tectum. An analysis of retinal patterning reveals that Meis1 is required to correctly specify both dorsal-ventral and nasal-temporal identity in the zebrafish retina. Meis1-knockdown results in a loss of smad1 expression and an upregulation in follistatin expression, thereby causing lower levels of Bmp signalling and a partial ventralization of the retina. Additionally, Meis1-deficient embryos exhibit ectopic Fgf signalling in the developing retina and a corresponding loss of temporal identity. Meis1 also positively regulates ephrin gene expression in the tectum. Consistent with these patterning phenotypes, a knockdown of Meis1 ultimately results in retinotectal mapping defects.ConclusionsIn this work we describe a novel role for Meis1 in regulating Bmp signalling and in specifying temporal identity in the retina. By patterning both the retina and tectum, Meis1 plays an important role in establishing the retinotectal map and organizing the visual system.
Highlights
IntroductionMultiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum
During visual system development, multiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum
To test if fsta can inhibit endogenous Gdf6a signalling in the zebrafish retina, we injected 100 pg of fsta mRNA into a single cell of twocell embryos and examined the level of phosphoSmads1/5/8 at 14 hpf by whole-mount immunohistochemistry. This asymmetrical injection of fsta mRNA causes uniocular reductions of phospho-Smads1/5/8 (n = 5/8; Figure 5F, G). These results suggest that follistatin a (Fsta) can inhibit Gdf6a-mediated signalling, and that the upregulation of fsta expression in meis1 morphants may contribute to the retinal DV patterning defects observed in these embryos
Summary
Multiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum. This information is required for the topographic mapping of retinal ganglion cell axons on the tectum. Retinotopic mapping has been most extensively studied in the optic tectum of fish, amphibians, and chick, and in the superior colliculus of mice Within both the retina and the tectum, axially restricted expression of the Eph and Ephrin families of axon guidance molecules provides some of the positional information required for retinotectal map formation. Axial patterning of the retina is required to establish the correct domains of Eph and Ephrin expression. Restricted ephrinB and ephB expression along the DV axis is required for normal formation of the retinotectal map [18,19]
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