Fig. 10. Role of NGNs in the specification of neuronal identity in the PNS. (A) Summary of the results obtained with NGN1 retrovirus in dNT cells (left) and NCSCs (right). (B) Model to explain results obtained in dNT cultures. IDS1, n indicates postulated sensory neuron identity co-determinants; IDAn indicates postulated autonomic identity co-determinants; the former are thought to be induced by low, and the latter by high concentrations of BMP2 (Fig. 3). The existence of such identity co-determinants is inferred from the fact that BMP2 dominantly controls the neuronal subtype promoted by NGNs, depending on its concentration (Fig. 6 and Table 2). The fact that NGNs can significantly enhance either sensory or autonomic differentiation above that in control GFP-infected cells (Fig. 6) implies that NGNs promote either the expression and/or function of the collaborating identity co-determinants. Blunt symmetrical arrows: the reciprocal inhibition between sensory and autonomic identity co-determinants is inferred from the fact that NGN1 promotes sensory and autonomic fates in a mutually exclusive manner at 25 ng/ml (Fig. 7). The induction of NGNs by BMP2 (broken arrow) is inferred from the observation that increasing BMP2 concentrations enhance the expression of endogenous NGN2. MASH1 promotes autonomic but not sensory neurogenesis at all concentrations of BMP2, because it cannot upregulate, or collaborate with, sensory identity co-determinants.
