Spatial regulation of amacrine cell genesis by Semaphorin 3f

Purpose: The axonal projections of retinal ganglion cells (RGCs) of the eye are topographically organized so that spatial information from visual images is preserved. This retinotopic organization is established during devel-opment by secreted morphogens that pattern domains of transcription factor expression within naso-temporal and dorso-ventral quadrants of the embryonic eye. Poorly understood are the downstream signaling molecules that generate the topographically organized retinal cells and circuits. The secreted signaling molecule Semaphorin 3fa (Sema3fa) belongs to the Sema family of molecules that provide positional information to developing cells. Here, we test a role for Sema3fa in cell genesis of the temporal zebrafish retina. Methods: We compare retinal cell genesis in wild type and sema3fa CRISPR zebrafish mutants by in situ hybrid-ization and immunohistochemistry. Results: We find that mRNAs for sema3fa and known receptors, neuropilin2b (nrp2b) and plexina1a (plxna1a), are expressed by progenitors of the temporal, but not nasal zebrafish embryonic retina. In the sema3fa(ca304/ca304) embryo, initially the domains of expression for atoh7 and neurod4, transcription factors necessary for the speci-fication of RGCs and amacrine cells, respectively, are disrupted. Yet, post-embryonically only amacrine cells of the temporal retina are reduced in numbers, with both GABAergic and glycinergic subtypes affected. Conclusions: These data suggest that Sema3fa acts early on embryonic temporal progenitors to control in a spatially-dependent manner the production of amacrine cells, possibly to allow the establishment of neural cir-cuits with domain-specific functions. We propose that spatially restricted extrinsic signals in the neural retina control cell genesis in a domain-dependent manner.

Automated summary

This study investigates the role of the secreted signaling molecule Sema3fa in the development of zebrafish retina. The results indicate that Sema3fa acts on temporal progenitors during embryogenesis to control the production of amacrine cells, possibly for the establishment of neural circuits with domain-specific functions.