Abstract
The earliest known determinants of retinal nasotemporal identity are the transcriptional regulators Foxg1, which is expressed in the prospective nasal optic vesicle, and Foxd1, which is expressed in the prospective temporal optic vesicle. Previous work has shown that, in zebrafish, Fgf signals from the dorsal forebrain and olfactory primordia are required to specify nasal identity in the dorsal, prospective nasal, optic vesicle. Here, we show that Hh signalling from the ventral forebrain is required for specification of temporal identity in the ventral optic vesicle and is sufficient to induce temporal character when activated in the prospective nasal retina. Consequently, the evaginating optic vesicles become partitioned into prospective nasal and temporal domains by the opposing actions of Fgfs and Shh emanating from dorsal and ventral domains of the forebrain primordium. In absence of Fgf activity, foxd1 expression is established irrespective of levels of Hh signalling, indicating that the role of Shh in promoting foxd1 expression is only required in the presence of Fgf activity. Once the spatially complementary expression of foxd1 and foxg1 is established, the boundary between expression domains is maintained by mutual repression between Foxd1 and Foxg1.
Highlights
Our ability to perceive the world around us and to represent visual information accurately requires correctly mapped innervation of the primary visual centres in the brain by retinal ganglion cell (RGC) axons
We show that Shh activity is required to activate foxd1 expression and to initiate temporal retinal identity at the onset of optic vesicle evagination in the zebrafish
This study uncovers a novel role for Shh in initiating the expression of the temporal fate determinant foxd1 in the ventral half of the evaginating optic vesicles
Summary
Our ability to perceive the world around us and to represent visual information accurately requires correctly mapped innervation of the primary visual centres in the brain by retinal ganglion cell (RGC) axons. Cyclopamine+SU5402 treatments from mid-gastrulation result in a dramatic expansion of foxd and complete loss of foxg expression within the optic vesicle (Fig. 4I,J), a phenotype comparable to that obtained by treatment with SU5402 alone [treatment from midgastrulation with only one drug at a time led to phenotypes very similar to those obtained with treatments at 1ss (not shown)] This result supports the idea that Hh activity is fully dispensable for induction of foxd expression in the absence of Fgf signalling. Cavefish optic vesicles show similar levels of foxg and foxd expression compared with surface fish (Fig. 4K-N), indicating that concomitant upregulation of the Hh and Fgf pathways does not overtly affect NT patterning Together, these results support the idea that it is the relative, rather than the absolute, levels of these two signals that influence the establishment of NT identity. The only position at which transcriptional crossregulatory competition between Foxd and Foxg is likely to influence foxg and foxd expression is around the NT boundary where cells may receive sufficient Shh and Fgf signals to induce both genes
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