Adrenergic differentiation of cells of the cholinergic ciliary and Remak ganglia in avian embryo after in vivo transplantation.

Abstract

We have previously shown that the neural crest is regionalized early into "adrenergic" and "cholinergic" areas from which arise, respectively, the sympathetic and parasympathetic ganglioblasts of the autonomic nervous system. This regionalization does not correspond, however, to an irreversible determination of the neural crest cells since, under certain experimental conditions, cholinergic cells can arise from the adrenergic region of the crest and vice versa. The phenotypic expression of the presumptive ganglion cells appears to be responsive to the environmental conditions they encounter during and/or after their migration. In the present study we show that the developmental behavior of parasympathetic ganlion cells which have stopped migrating and at least some of which have started to differentiate into cholinergic neurons can be profoundly modified if they are transplanted into a younger embryo at the trunk neural crest level. The grafted ganglion cells start migrating and stop in the same sites as the host neural crest cells. Their further differentiation depends on their localization.When situated in the adrenergic ganglia and in the suprarenal gland they synthesize catecholamines, whereas they differentiate into nonfluorescent, silver-staining ganglion cells if they migrate in the gut wall. Thus, the differentiation of autonomic neurons is dependent on tissue interactions even after the neural crest cells have grouped to form ganglionic structures in which biochemical differentiation is already in progress. The ganglion cells of the autonomic nervous system arise from the neural crest. Using a cell-marking technique by means of which the migration of the neural crest cells can be followed in the developing avian embryo, we have been able to identify various regions in the neural axis according to their role in the formation of the autonomic nervous system: one gives rise to the cholinergic enteric ganglia, another participates in the constitution of the sympathetic adrenergic ganglia and the adrenomedulla, and two areas produce both adrenergic and cholinergic cells (Fig. 1) (1-3).The presumptive fate of the ganglioblasts originating from the regions so defined is not irreversibly fixed. The migration pattern of the crest cells can be changed by transplanting the "vagal" region of the neural crest at the "adrenomedullary" level and vice versa. Under these conditions, presumptive adrenergic ganglioblasts migrate into the gut and differentiate there into fully functional cholinergic ganglia, while cephalic neural crest cells colonize the suprarenal gland and develop into adrenomedullary cells (4-6). Therefore, the capacity for developing into cholinergic and adrenergic ganglion and paraganglion cells appears widespread in the whole neural crest (2, 3), the expression of either one or the other phenotype being dependent on the tissue environment to which the cells are subsequently subjected. Moreover, the plasticity of young auThe costs of publication of this article were defrayed in part by the pa...

Molecular control of ciliary neuron development: BMPs and downstream transcriptional control in the parasympathetic lineage

“…Heterotopic neural crest transplantation experiments demonstrated that the developmental capacities of the neural crest cells are qualitatively equivalent at all axial levels (Le Dourin et al, 1975;Le Douarin and Kalcheim, 1999), which strongly suggest that local signals specify the fate of neural crest cells following their migration. The finding that autonomic precursor cells are present in the ciliary ganglion at E4.5 and later that can differentiate to noradrenergic neurons upon heterotopic transplantation (Le Douarin et al, 1978;Dupin, 1984) seems to contradict our inability to elicit noradrenergic differentiation by BMP4 overexpression. It should, however, be noted that the potential of these cells is repressed during normal development, apparently by local signals, and is revealed and realized only after ganglia disassemble during backtransplantation (Le Douarin et al, 1978;Dupin, 1984;Schweizer et al, 1983).…”

“…The finding that autonomic precursor cells are present in the ciliary ganglion at E4.5 and later that can differentiate to noradrenergic neurons upon heterotopic transplantation (Le Douarin et al, 1978;Dupin, 1984) seems to contradict our inability to elicit noradrenergic differentiation by BMP4 overexpression. It should, however, be noted that the potential of these cells is repressed during normal development, apparently by local signals, and is revealed and realized only after ganglia disassemble during backtransplantation (Le Douarin et al, 1978;Dupin, 1984;Schweizer et al, 1983). Thus, we propose that the local environmental, signals that define parasympathetic neuron identity in the ciliary ganglion primordium e.g.…”

Colonization of the bowel by neural crest‐derived cells re‐migrating from foregut backtransplanted to vagal or sacral regions of host embryos

“…Recent experiments have suggested that many crestderived cells remain uncommitted at the time they first arrive in the gut. These experiments utilized the technique of backtransplantation, in which tissue containing developing ganglia is grafted to a younger embryonic host (Le Douarin et al, 1978). When this is done, some of the crest-derived cells in the donor's ganglia recover the ability of their ancestors to migrate and follow neural crest migration pathways in the host embryos.…”

Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain.

“…The different constructs were transfected into COS cells and 3 days later conditioned medium was tested for biological activity in bioassays that measured fiber outgrowth from various chicken embryo ganglia. A marked stimulation of neurite outgrowth, consistently resulting in circular or oval fiber halos, was seen in the ganglion ofRemak, a ganglionated nerve trunk in the mesorectum ofthe chicken embryo (38,39) (Fig. 4a).…”