Regulation of retinal axon growth by secreted Vax1 homeodomain protein

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Retinal ganglion cell (RGC) axons of binocular animals cross the midline at the optic chiasm (OC) to grow toward their synaptic targets in the contralateral brain. Ventral anterior homeobox 1 (Vax1) plays an essential role in the development of the OC by regulating RGC axon growth in a non-cell autonomous manner. Here, we identify an unexpected function of Vax1 that is secreted from ventral hypothalamic cells and diffuses to RGC axons, where it promotes axonal growth independent of its transcription factor activity. We demonstrate that Vax1 binds to extracellular sugar groups of the heparan sulfate proteoglycans (HSPGs) located in RGC axons. Both Vax1 binding to HSPGs and subsequent penetration into the axoplasm, where Vax1 activates local protein synthesis, are required for RGC axonal growth. Together, our findings demonstrate that Vax1 possesses a novel RGC axon growth factor activity that is critical for the development of the mammalian binocular visual system.
Publisher
ELIFE SCIENCES PUBLICATIONS LTD
Issue Date
2014-09
Language
English
Article Type
Article
Keywords

HEPARAN-SULFATE PROTEOGLYCAN; HOMEOBOX-CONTAINING GENE; GANGLION-CELL AXONS; OPTIC CHIASM; ENGRAILED HOMEOPROTEIN; VISUAL-SYSTEM; NR-CAM; GUIDANCE; EXPRESSION; PLASTICITY

Citation

ELIFE, v.3

ISSN
2050-084X
DOI
10.7554/eLife.02671
URI
http://hdl.handle.net/10203/194695
Appears in Collection
BS-Journal Papers(저널논문)
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