Platelet-derived growth factor is constitutively secreted from neuronal cell bodies but not from axons

Neurons synthesise and secrete many growth and survival factors but it is n ot usually clear whether they are released locally at the cell body or furt her afield from axons or axon terminals. Without this information, we canno t predict the site(s) of action or the biological functions of many neuron- derived factors. for example, can neuronal platelet-derived growth factor ( PDGF) be secreted from axons and reach glial cells in nerve-fibre (white-ma tter) tracts? To address this question, we expressed PDGF-A in retinal gang lion neurons in transgenic mice and tested for release of PDGF from cell bo dies in the retina and from axons in the optic nerve. In both the retina an d optic nerve, there are glial cells that express PDGF receptor alpha (PDGF R alpha) [1] and divide in response to PDGF [2-5], so we could detect funct ional PDGF indirectly through the mitogenic response of glia at both locati ons. Expressing PDGF-A in neurons under the control of the neuron-specific enolase promoter (NSE-PDGF-A) resulted in a striking hyperplasia of retinal astrocytes, demonstrating that PDGF is secreted from the cell bodies of ne urons in the retina [4], In contrast, glial proliferation in the optic nerv e was unaffected, indicating that PDGF is not released from axons, When PDG F was expressed directly in the optic nerve under the control of an astrocy te-specific promoter (GFAP-PDGF-A), oligodendrocyte progenitors hyperprolif erated, resulting in a hypertrophic optic nerve. We conclude that PDGF is c onstitutively secreted from neuronal cell bodies in vivo, but not from axon s in white-matter tracts.