Transcriptional control of visual neural circuit development by GS homeobox 1

Abstract

As essential components of gene expression networks, transcription factors regulate neural circuit assembly. GS homeobox 1 (gsx1) is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons terminate in ten arborization fields (AFs) in the optic tectum (TeO) and pretectum (Pr). Pretectal AFs (AF1-AF9) mediate distinct and essential visual behaviors, yet we understand less about their development compared to AF10 in the TeO. Using gsx1 zebrafish mutants, immunohistochemistry, and transgenic lines, we observed that gsx1 is required for vesicular glutamate transporter, slc17a6b, expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet exhibit impaired vision and a significantly reduced volume of RGC axons innervating the Pr and TeO, including loss of AF7. Consistent with this, prey capture is reduced in gsx1 mutants. Timed laser ablation of slc17a6b-positive neurons reveals that they aide directly in AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system. SUMMARY STATEMENTThis is the first study in any vertebrate model to establish a requirement for the homeobox transcription factor encoding gene, gsx1, in visual neural circuit formation and function.