Autonomic neurogenesis and apoptosis are alternative fates of progenitor cell communities induced by TGF beta

The question of how appropriate cell types are generated in correct numbers during development of the peripheral nervous system has become particularl y intriguing with the identification of multipotent progenitor cells in pos tmigratory targets of the neural crest. Recently, we have provided evidence that community effects in response to factors of the TGF beta family might represent a mechanism to suppress inappropriate nonneural fates from multi potent progenitors in developing peripheral ganglia. In culture, BMP2 and T GF beta promote neurogenesis at the expense of a smooth-muscle-like fate in clusters of neural-crest-derived multipotent progenitor cells. We now show that the neurons generated by TGF beta factors belong to the autonomic lin eage and that cells within the developing sympathetic ganglia express TGF b eta -type II receptor. In addition to its neurogenic activity, TGF beta but not BMP2 also induces apoptosis as an alternative fate in cultured progeni tor communities. Interestingly, these fate decisions are controlled by grad ed changes in TGF beta concentrations: lower doses of TGF beta promote neur ogenesis while slightly higher doses induce predominantly apoptosis. These effects of TGF beta are specific for an early developmental stage since pro genitor cells lose their competence to respond to the proapoptotic activity of TGF beta upon neuronal differentiation. In vivo, the expression of TGF beta3 in differentiated neurons suggests that the signal concentration grad ually increases with the number of neurons formed in the autonomic ganglia. We propose that TGF beta functions in a biphasic manner during autonomic g angliogenesis to control both neurogenesis and subsequently the number of n eurons generated from progenitor cells. (C) 2000 Academic Press.