The development of cholinergic sympathetic neurons: a role for neuropoietic cytokines?

The sympathetic neurons that innervate eccrine sweat glands undergo a phenotypic switch from noradrenergic to cholinergic and peptidergic. The changes in neurotransmitter choice are retrogradely specified by interactions with the target tissue that are mediated by a secreted differentiation factor. Production of the target-derived differentiation factor requires noradrenergic innervation. The switch from noradrenergic to cholinergic and peptidergic is reproduced in culture when neonatal sympathetic neurons are treated with members of the neuropoietic cytokine family, leukemia inhibitory factor (LIF) or ciliary neurotrophic factor (CNTF), suggesting that these cytokines might be responsible for the target-induced change in neurotransmitter properties. Analysis of transgenic mice that lack either LIF or CNTF or both, however, does not support their candidacy: the transmitter properties of the sweat gland innervation is indistinguishable from that of wild-type mice. It seems likely that another and novel member of the, family is responsible.