New way to construct cross roads in the brain
Recent research by scientists in the Department of Biology at KAIST involving the discovery of a different activity of Vax1 has allowed for a better understanding of how vision can be made possible. Furthermore, a revision of the previous view of homeodomain transcription factors has been made possible.
The season of the welcoming and frothy cherry blossoms visited the KAIST campus again this year. The beautiful images of light pink flowers “pour” into our two eyes and are stored in our brain. As with humans, all vertebrates possess binocular eyes; their optical nerves cross in the brain, to deliver images into both sides of the brain.
It enables a stereoscopic perception. Though these means help discriminate objects near and far, the mechanism underlying the development of the optic chiasm, which is a crossing point of the optic nerve in the brain, has remained unknown until recently.
Researchers have identified ventral anterior homeobox 1 (VAX1) that acts in the retinal axon after being secreted from the ventral hypothalamic radial glia to facilitate axonal growth toward the brain midline (Kim et al., eLife (2014)).
The researchers have recognized homeodomain-containing proteins as transcription factors owing to the DNA binding ability of the homeodomain. This was also to VAX1, essential for the development of commissures in human and mouse brain.
However, this study shows that mouse Vax1 regulates retinal axon growth toward the ventral hypothalamic area in a transcription activity-independent manner. More surprisingly, Vax1 was detectable in the retinal axon, which does not express the Vax1 gene at all, suggesting that the Vax1 proteins in the axons might be derived from external sources including the ventral hypothalamic glia that express the Vax1 gene.
This hypothesis was proved in various systems and also identified heparan sulfate proteoglycan (HSPG) as receptors that capture extracellular Vax1, which then deliver it into the retinal axons. Moreover, the researchers found that the externally-derived Vax1 in the retinal axons plays a role as a translation regulator but not as a transcription factor.
The finding of this unconventional and non-orthodox activity of Vax1 in the binocular visual system development not only helps in understanding the development of the optic chiasm, but it also revises the classical view of the roles of homeodomain transcription factors. After this discovery, the screening for homeodomain proteins that share a novel ability for intercellular transfer was initiated, and >40 strong candidates have been found, which are awaiting future study. Please cross your fingers on this journey that seeks remote acting transcription factors!