TY - JOUR TI - Regulation of retinal axon growth by secreted Vax1 homeodomain protein AU - Kim, Namsuk AU - Min, Kwang Wook AU - Kang, Kyung Hwa AU - Lee, Eun Jung AU - Kim, Hyoung-Tai AU - Moon, Kyunghwan AU - Choi, Jiheon AU - Le, Dai AU - Lee, Sang-Hee AU - Kim, Jin Woo A2 - Bronner, Marianne E VL - 3 PY - 2014 DA - 2014/09/08 SP - e02671 C1 - eLife 2014;3:e02671 DO - 10.7554/eLife.02671 UR - https://doi.org/10.7554/eLife.02671 AB - 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. In this study, 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. KW - ventral anterior homeobox 1 (Vax1) KW - retinal axon growth KW - optic chiasm KW - intercellular protein transfer JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -