NEURTURIN AND GDNF PROMOTE PROLIFERATION AND SURVIVAL OF ENTERIC NEURON AND GLIAL PROGENITORS IN-VITRO

Signaling through the c-Ret tyrosine kinase and the endothelin B recep tor pathways is known to be critical for development of the enteric ne rvous system. To clarify the role of these receptors in enteric nervou s system development, the effect of ligands for these receptors was ex amined on rat enteric neuron precursors in fully definedd medium in pr imary culture. In this culture system, dividing Ret-positive cells dif ferentiate, cluster into ganglia containing neurons and enteric glia, and create extensive networks reminiscent of the enteric plexus establ ished in vivo. Glial cell-line-derived neurotrophic factor (GDNF) and neurturin both potently support survival and proliferation of enteric neuron precursors in this system. Addition of either neurturin or GDNF to these cultures increased the number of both neurons and enteric gl ia. Persephin, a third GDNF family member, shares many properties with neurturin and GDNF in the central nervous system and in kidney develo pment. By contrast, persephin does not promote enteric neuron precurso r proliferation or survival in these cultures. Endothelin-3 also does not increase the number of enteric neurons or glia in these cultures. (C) 1998 Academic Press.