Artemin (ART) signals through the GFRα-3/RET receptor complex to support sympathetic neuron development. Here we show that ART also influences autonomic elements in adrenal medulla and enteric and pelvic ganglia. Transgenic mice over-expressing Art throughout development exhibited systemic autonomic neural lesions including fusion of adrenal medullae with adjacent paraganglia, adrenal medullary dysplasia, and marked enlargement of sympathetic (superior cervical and sympathetic chain ganglia) and parasympathetic (enteric, pelvic) ganglia. Changes began by gestational day 12.5 and formed progressively larger masses during adulthood. Art supplementation in wild type adult mice by administering recombinant protein or an Art-bearing retroviral vector resulted in hyperplasia or neuronal metaplasia at the adrenal corticomedullary junction. Expression data revealed that Gfrα-3 is expressed during development in the adrenal medulla, sensory and autonomic ganglia and their projections, while Art is found in contiguous mesenchymal domains (especially skeleton) and in certain nerves. Intrathecal Art therapy did not reduce hypalgesia in rats following nerve ligation. These data (1) confirm that ART acts as a differentiation factor for autonomic (chiefly sympathoadrenal but also parasympathetic) neurons, (2) suggest a role for ART overexpression in the genesis of pheochromocytomas and paragangliomas, and (3) indicate that ART is not a suitable therapy for peripheral neuropathy.

The layer of cytoplasm underlying the plasmalemma of Xenopus eggs has contractile activity which is of vital importance in fertilization and early development, being involved in such processes as sperm engulfment, cortical granule exocytosis, development of the axes of embryonic symmetry and cleavage. In amphibian eggs this layer is also involved in wound healing and changes of cellular shape at gastrulation. Two kinds of contractile structures can be distinguished near the surface of Xenopus eggs. To characterize the mechanism and regulation of this contractile activity, we have experimentally induced cortical contractions in bisected living Xenopus eggs. We have shown previously that cortical contractions are induced by calcium ions in the bisected egg. Here we show that extraction of soluble cytoplasmic components prevents the calcium-induced contractions, but that addition of exogenous soluble myosin restores them. In oocytes, both soluble and insoluble components of the cortical cytoplasm are unable to support contraction. Thus, during meiotic maturation of oocytes into eggs, both of the components of the cortical cytoplasm must change so as to become competent for contraction.

No abstract