Multiple effects of artemin on sympathetic neurone generation, survival and growth

To define the role of artemin in sympathetic neurone development, we have s tudied the effect of artemin on the generation, survival and growth of symp athetic neurones in low-density dissociated cultures of mouse cervical and thoracic paravertebral sympathetic ganglia at stages throughout embryonic a nd postnatal development. Artemin promoted the proliferation of sympathetic neuroblasts and increased the generation of new neurones in cultures estab lished from E12 to E14 ganglia. Artemin also exerted a transient survival-p romoting action on newly generated neurones during these early stages of de velopment. Between E16 and P8, arternin exerted no effect on survival, but by P12, as sympathetic neurones begin to acquire neurotrophic factor indepe ndent survival, artemin once again enhanced survival, and by P20 it promote d survival as effectively as nerve growth factor (NGF). During this late pe riod of development, arternin also enhanced the growth of neurites from cul tured neurones more effectively than NGF. Confirming the physiological rele vance of the mitogenic action of artemin on cultured neuroblasts, there was a marked reduction in the rate of neuroblast proliferation in the sympathe tic ganglia of mice lacking the GFR alpha3 subunit of the arternin receptor . These results indicate that artemin exerts several distinct effects on th e generation, survival and growth of sympathetic neurones at different stag es of development.