Draxin from neocortical neurons controls the guidance of thalamocortical projections into the neocortex

Abstract

The thalamocortical tract carries sensory information to the neocortex. It has long been recognized that the neocortical pioneer axons of subplate neurons are essential for thalamocortical development. Herein we report that an axon guidance cue, draxin, is expressed in early-born neocortical neurons, including subplate neurons, and is necessary for thalamocortical development. In draxin−/− mice, thalamocortical axons do not enter the neocortex. This phenotype is sufficiently rescued by the transgenic expression of draxin in neocortical neurons. Genetic interaction data suggest that draxin acts through Deleted in colorectal cancer (DCC) and Neogenin (Neo1), to regulate thalamocortical projections in vivo. Draxin promotes the outgrowth of thalamic axons in vitro and this effect is abolished in thalamic neurons from Dcc and Neo1 double mutants. These results suggest that draxin from neocortical neurons controls thalamocortical projections into the neocortex, and that this effect is mediated through the DCC and Neo1 receptors.

Understanding axon guidance: are we nearly there yet?

“…However, this is not expected as very few new guidance cues have been discovered over the last decade or so. Draxin, a secreted protein that has no homology with other previously identified guidance cues, was identified as a repellent for axons in the developing brain and spinal cord (Islam et al, 2009;Shinmyo et al, 2015;Ahmed et al, 2011), and a guidance function was recently demonstrated for phosphatidyl-β-D-glucoside and its derivative lyso-phosphatidyl-β-D-glucoside (LysoPtdGlc) expressed on glial cells in the dorsal spinal cord (Guy et al, 2015).…”

Genomic characterisation and conservation genetics of the indigenous Irish Kerry cattle breed

“…A single gene was located within the BTA9 selection peak—the phosphodiesterase 7B gene ( PDE7B ), which has been associated with neurobiological processes (de Gortari and Mengod, 2010) and has been previously linked to genetic changes associated with dog ( Canis lupus familiaris ) domestication and behaviour (Freedman et al, 2016). A single gene was also located within the BTA16 selection peak—the dorsal inhibitory axon guidance protein gene ( DRAXIN ), which encodes a protein that regulates axon guidance, neural circuit formation and vertebrate brain development (Islam et al, 2009; Shinmyo et al, 2015). Twenty-four genes were located within the BTA17 selection peak, including BICDL1 , RAB35 and RNF10 , which have been associated with neurobiology and brain development (Hoshikawa et al, 2008; Schlager et al, 2010; Villarroel-Campos et al, 2016) and SIRT4 and COQ5 that function in cellular metabolism (Kawamukai, 2015; Elkhwanky and Hakkola, 2017).…”

Thalamic neuronal specification and early circuit formation

“…The protein promotes axon outgrowth when applied to dissociated thalamic neurons in a DCC and Neo1 dependent fashion. Additionally, compound mutants of Dcc and Neo1 show similar axonal phenotypes as Draxin null mutants in vivo (Shinmyo et al, ). This indicates that Dcc expressed by thalamic axons are important at several steps during the TCA pathfinding.…”

“…The binding partner of Linx expressed on TCAs remains to be determined. Recently, Draxin expressed by cortical cells was shown necessary for TCAs to cross the PSB and enter into the cortex after passing the corridor (Shinmyo et al, ). The protein promotes axon outgrowth when applied to dissociated thalamic neurons in a DCC and Neo1 dependent fashion.…”