Sema4D stimulates axonal outgrowth of embryonic DRG sensory neurones.

Several semaphorins are thought to function as potent inhibitors of axonal growth. We have found that Sema4D stimulates axonal outgrowth of embryonic dorsal root ganglion (DRG) neurones in stead of retraction. Neutralizing antibodies to Sema4D inhibit this action. This action appears to differ slightly from that on PC12 cells, because DRG neurones respond to Sema4D without addition of nerve growth factor (NGF), while PC12 cells do not. On the other hand, it is blocked by deprivation of endogenous NGF with antibodies to NGF and also by Trk-inhibitor K252a, suggesting that endogenously produced-NGF and the activation of Trk receptor are required for Sema4D-action on DRG neurones. These indicate that neurite-outgrowth promoting actions of Sema4D are similar between DRG neurones and PC12 cells, since NGF-Trk signalling are required for these actions. Since Schwann cells can produce NGF, the contamination of these cells in our DRG culture might explain this action. In addition to plexin-B1 that is known as a Sema4D receptor, binding experiments indicate plexin-B2 as another receptor candidate for Sema4D. These plexins and Sema4D are expressed in embryonic DRGs. We suggest a new function of Sema4D as a neurite-outgrowth stimulating, autocrine/paracrine factor in embryonic sensory neurones.