Transcriptional control of visual neural circuit development by GS homeobox 1.

As essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene, 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 that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr), and thalamus. Pretectal AFs (AF1-AF9) mediate distinct 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, Tg(slc17a6b:DsRed), expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet they exhibit impaired visual ability during prey capture. RGC axon volume in the gsx1 mutant Pr and TeO is reduced, and AF7 that is active during feeding is missing which is consistent with reduced hunting performance. Timed laser ablation of Tg(slc17a6b:DsRed)-positive cells reveals that they are necessary for AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system.

Gsx2, but not Gsx1, is necessary for early forebrain patterning and long-term survival in zebrafish.

BACKGROUND: Homeobox transcription factor encoding genes, genomic screen homeobox 1 and 2 (gsx1 and gsx2), are expressed during neurodevelopment in multiple vertebrates. However, we have limited knowledge of the dynamic expression of these genes through developmental time and the gene networks that they regulate in zebrafish. RESULTS: We confirmed that gsx1 is expressed initially in the hindbrain and diencephalon and later in the optic tectum, pretectum, and cerebellar plate. gsx2 is expressed in the early telencephalon and later in the pallium and olfactory bulb. gsx1 and gsx2 are co-expressed in the hypothalamus, preoptic area, and hindbrain, however, rarely co-localize in the same cells. gsx1 and gsx2 mutant zebrafish were made with TALENs. gsx1 mutants exhibit stunted growth, however, they survive to adulthood and are fertile. gsx2 mutants experience swim bladder inflation failure that prevents survival. We also observed significantly reduced expression of multiple forebrain patterning distal-less homeobox genes in mutants, and expression of foxp2 was not significantly affected. CONCLUSIONS: This work provides novel tools with which other target genes and functions of Gsx1 and Gsx2 can be characterized across the central nervous system to better understand the unique and overlapping roles of these highly conserved transcription factors.