Nj. Francis et al., CNTF AND LIF ARE NOT REQUIRED FOR THE TARGET-DIRECTED ACQUISITION OF CHOLINERGIC AND PEPTIDERGIC PROPERTIES BY SYMPATHETIC NEURONS IN-VIVO, Developmental biology, 182(1), 1997, pp. 76-87
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.