CNTF AND LIF ARE NOT REQUIRED FOR THE TARGET-DIRECTED ACQUISITION OF CHOLINERGIC AND PEPTIDERGIC PROPERTIES BY SYMPATHETIC NEURONS IN-VIVO

During development, the sympathetic innervation of two targets, sweat glands and periosteum, changes the neurotransmitters it expresses from noradrenaline to acetylcholine and vasoactive intestinal peptide (VIP ). The target-derived molecules that induce these changes have not bee n identified. Neuropoietic cytokines, including ciliary neurotrophic f actor (CNTF) and leukemia inhibitory factor (LIF), induce the same phe notypic changes in sympathetic neurons in vitro as sweat glands and pe riosteum do in vivo, raising the possibility that one of these factors mediates induction of cholinergic traits and VIP by these target tiss ues. Because CNTF and LIF have overlapping functions and signalling pa thways, they could act interchangeably or in concert to influence neur otransmitter expression. To determine whether CNTF or CNTF and LIF tog ether are responsible for the induction of cholinergic and peptidergic function in vivo, we analyzed the neurotransmitter properties of swea t gland innervation in mice lacking CNTF or CNTF and LIF. We find that , as in wild-type mice, gland innervation in mice lacking one or both molecules appropriately expresses cholinergic properties and VIP immun oreactivity. Furthermore, footpads of mice lacking one or both genes c ontain choline acetyltransferase activity comparable to that of wild-t ype mice, and CNTF- or CNTF/LIF-deficient mice possess the normal comp lement of active sweat glands. We analyzed the innervation of a second , recently identified cholinergic sympathetic target, the periosteum, which is the connective tissue surrounding bone. Periosteal innervatio n of mice lacking CNTF, LIF, or both, like that of wild-type mice, is immunoreactive for the vesicular acetylcholine transporter, a recently identified cholinergic marker, and VIP. These results provide evidenc e that neither CNTF, LIF, nor a combination of the two are required fo r the developmental change from noradrenergic to cholinergic function that occurs in sympathetic innervation of sweat glands and periosteum. (C) 1997 Academic Press.