Target-dependent specification of the neurotransmitter phenotype:cholinergic differentiation of sympathetic neurons is mediated in vivo by gp130 signaling

Abstract

Sympathetic neurons are generated through a succession of differentiation steps that initially lead to noradrenergic neurons innervating different peripheral target tissues. Specific targets, like sweat glands in rodent footpads, induce a change from noradrenergic to cholinergic transmitter phenotype. Here, we show that cytokines acting through the gp130 receptor are present in sweat glands. Selective elimination of the gp130 receptor in sympathetic neurons prevents the acquisition of cholinergic and peptidergic features (VAChT, ChT1, VIP) without affecting other properties of sweat gland innervation. The vast majority of cholinergic neurons in the stellate ganglion, generated postnatally, are absent in gp130-deficient mice. These results demonstrate an essential role of gp130-signaling in the target-dependent specification of the cholinergic neurotransmitter phenotype.

The Sympathetic Neurotransmitter Switch Depends on the Nuclear Matrix Protein Satb2

“…Some neurons in rodent sympathetic ganglia are known to acquire cholinergic properties before birth at early embryonic stages Huber and Ernsberger, 2006). Studies in mice deficient for gp130, LIFR␤ (LIF receptor ␤), or CNTFR (CNTF receptor) have demonstrated that the embryonic cholinergic differentiation is not controlled by gp130 cytokines (Stanke et al, 2000(Stanke et al, , 2006. Consistently, our results show a lack of Satb2 expression during late embryonic or early postnatal stages.…”

“…This neurotransmitter plasticity occurs at postnatal stages in individual postmitotic neurons under the influence of neuropoietic cytokines, released by the target tissue after innervation (Landis, 1990(Landis, , 1996Stanke et al, 2006). The noradrenergic-to-cholinergic neurotransmitter switch can be induced in vitro in cultured sympathetic neurons by members of the neuropoietic cytokine family, such as ciliary neurotrophic factor (CNTF) or leukemia inhibitory factor (LIF) (Fann and Patterson, 1994).…”

Dendrite Complexity of Sympathetic Neurons Is Controlled during Postnatal Development by BMP Signaling

“…Mice containing deletions in Bmpr1a or Smad4 in sympathetic neurons were obtained by crossing conditional lines to the DbhiCre (Stanke et al, 2006;Parlato et al, 2007) mouse line.…”

“…The Bmpr1a cKO and Bmpr1a cKO /1b ⌬ lines are in a mixed C57BL/ 6129SvEv genetic background (Yi et al, 2000;Parlato et al, 2007) with low 129SvEv contribution (Y. Mishina, personal communication). Smad4 ϩ/fl (Yang et al, 2002) are in a C57BL/6FVN mixed background and were repeatedly crossed with the DbhiCre line (C57BL6) (Stanke et al, 2006;Parlato et al, 2007) . Cell culture.…”

“…Antisense, digoxigenin-labeled riboprobes for Phox2b, Dbh, Th, Scg10, and Nf68 were generated by in vitro transcription according to the instructions of the manufacturer (Dig-nucleic-acid-detection-kit; Roche Diagnostics). In situ hybridization was performed as previously described (Ernsberger et al, 1997;Stanke et al, 1999).…”