Bone morphogenetic protein-2 and retinoic acid induce neurotrophin-3 responsiveness in developing rat sympathetic neurons

Kobayashi, Miwako; Fujii, Miyuki; Kurihara, Kenzo; Matsuoka, Isao

doi:10.1016/s0169-328x(97)00291-x

Cited by 39 publications

(45 citation statements)

References 35 publications

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“…On the other hand, studies using in vitro culture system indicate that GDNF and NT3, when added separately, support survival of the SCG neurons from perinatal rats to a lower extent: 5-20% of the plated neurons. This is much less than that supported by NGF (Ͼ80% of the plated neurons) Kobayashi et al, 1998). These studies suggest that environmental factor(s) are necessary for SCG neurons to maintain responsiveness to GDNF and NT3.…”

Section: Abstract: Neurotrophic Factor; Gdnf; Gfr␣-1; Bmp2; Retinoicmentioning

confidence: 69%

“…Sympathetic neurons were cultured according to the method described previously (Kobayashi et al, 1998). SCG were dissected from Wistar rats at embryonic day 17 (E17) and sequentially digested with collagenase (3 mg /ml; Sigma) for 30 min and trypsin (2 mg /ml; Difco, Detroit, M I) for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…Neurotrophin (Bothwell, 1995) and glial cell line-derived neurotrophic factor (GDNF) (Olson, 1997) families are two major gene families of neurotrophic factors. Although the mechanisms for the acquisition of responsiveness to members of neurotrophin family have been well investigated (Wyatt and Davies, 1993;Robinson et al, 1996;Holst et al, 1997;Kobayashi et al, 1998;Zhang et al, 1998;Wyatt et al, 1999), the mechanism for that of the GDNF family is not well known.…”

Section: Abstract: Neurotrophic Factor; Gdnf; Gfr␣-1; Bmp2; Retinoicmentioning

confidence: 99%

“…In the search for such environmental factors, we previously found cooperative roles of bone morphogenetic protein-2 (BMP2) and retinoic acid (RA) in the enhancement of NT3 responsiveness in SCG neurons (Kobayashi et al, 1998). Alteration of the Trk receptor expression from TrkA to TrkC by BMP2-RA indicates that cultured SCG neurons from perinatal rats keep the plasticity of responsiveness to neurotrophic factors and thus serve as a suitable model to study the mechanism of the developmental acquisition of the neurotrophic factor responsiveness.…”

Section: Abstract: Neurotrophic Factor; Gdnf; Gfr␣-1; Bmp2; Retinoicmentioning

confidence: 99%

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Regulation of Glial Cell Line-Derived Neurotrophic Factor Responsiveness in Developing Rat Sympathetic Neurons by Retinoic Acid and Bone Morphogenetic Protein-2

2000

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There are several lines of evidence suggesting that, in addition to neurotrophins, member(s) of glial cell line-derived neurotrophic factor (GDNF) family play important roles in the development of sympathetic neurons. However, the mechanism regulating the responsiveness of the neurons to GDNF family members is not known. Previously, we reported on the cooperative roles of bone morphogenetic protein-2 (BMP2) and retinoic acid (RA) in the enhancement of neurotrophin-3 (NT3) responsiveness in cultured sympathetic neurons dissociated from perinatal rat superior cervical ganglia (SCG). In the present study, we further examined the effects of BMP2 and RA on the regulation of the responsiveness of SCG neurons to GDNF family members. Consequently, we found that RA alone induced the responsiveness of SCG neurons specifically to GDNF by upregulating the ligand-specifying receptor for GDNF (GFR␣-1) at both the mRNA and protein levels. The expression levels of mRNAs for other ligand-specifying receptors for GDNF family (GFR␣-2 and GFR␣-3) were unaffected by RA. Although the upregulation of signal-transducing receptor Ret by the RA treatment was rather small, this treatment significantly increased the efficacy of tyrosine phosphorylation of Ret by GDNF. Experiments using synthetic retinoids suggested that RA acts through ␣-type of nuclear retinoic acid receptor to exert the induction of GDNF responsiveness. On the other hand, BMP2, which had no significant effect by itself on the GDNF responsiveness, promoted the action of RA to upregulate GFR␣-1 and enhance the GDNF responsiveness. These results indicate that RA and BMP2 play important roles in the induction of GDNF responsiveness, as well as NT3 responsiveness, of developing SCG neurons.

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Section: Abstract: Neurotrophic Factor; Gdnf; Gfr␣-1; Bmp2; Retinoicmentioning

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Section: Abstract: Neurotrophic Factor; Gdnf; Gfr␣-1; Bmp2; Retinoicmentioning

confidence: 99%

Section: Abstract: Neurotrophic Factor; Gdnf; Gfr␣-1; Bmp2; Retinoicmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Glial Cell Line-Derived Neurotrophic Factor Responsiveness in Developing Rat Sympathetic Neurons by Retinoic Acid and Bone Morphogenetic Protein-2

2000

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“…NGF signaling regulates the density and pattern of innervation of target tissues independent of effects on sensory neuron survival (Patel et al, 2000). Although there was no change in the level of neurotrophins in the skin at the ages examined, it is possible that there were changes in other elements of the neurotrophin signal transduction pathway (Kobayashi et al, 1998;Zhang et al, 1998) or changes in neurotrophins at other ages. In addition to an increase in the density of innervation in the skin of the noggin transgenic animals, there was a marked change in the pattern of innervation by different types of fibers.…”

Section: Discussionmentioning

confidence: 99%

Target-derived BMP signaling limits sensory neuron number and the extent of peripheral innervation in vivo

et al. 2004

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The role of target-derived BMP signaling in development of sensory ganglia and the sensory innervation of the skin was examined in transgenic animals that overexpress either the BMP inhibitor noggin or BMP4 under the control of a keratin 14 (K14) promoter. Overexpression of noggin resulted in a significant increase in the number of neurons in the trigeminal and dorsal root ganglia. Conversely, overexpression of BMP4 resulted in a significant decrease in the number of dorsal root ganglion neurons. There was no significant change in proliferation of trigeminal ganglion neurons in the noggin transgenic animals, and neuron numbers did not undergo the normal developmental decrease between E12.5 and the adult, suggesting that programmed cell death was decreased in these animals. The increase in neuron numbers in the K14-noggin animals was followed by an extraordinary increase in the density of innervation in the skin and a marked change in the pattern of innervation by different types of fibers. Conversely, the density of innervation of the skin was decreased in the BMP4 overexpressing animals. Further Merkel cells and their innervation were increased in the K14-noggin mice and decreased in the K14-BMP4 mice. The changes in neuron numbers and the density of innervation were not accompanied by a change in the levels of neurotrophins in the skin. These findings indicate that the normal developmental decrease in neuron numbers in sensory ganglia depends upon BMP signaling, and that BMPs may limit both the final neuron number in sensory ganglia as well as the extent of innervation of targets. Coupled with prior observations, this suggests that BMP signaling may regulate the acquisition of dependence of neurons on neurotrophins for survival, as well as their dependence on target-derived neurotrophins for determining the density of innervation of the target.

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Retinoic acid regulates the morphological development of sympathetic neurons

et al. 2000

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Interactions between all‐trans‐retinoic acid (RA) and bone morphogenetic proteins (BMPs) affect the expression of neurotrophin receptors in sympathetic neurons (Kobayashi et al., 1998). In this study, we examined the possibility that similar interactions might regulate the morphological development of these neurons. Under control conditions, embryonic rat sympathetic neurons formed axons but not dendrites; cells exposed to RA had a similar appearance. Profuse dendritic growth was observed upon exposure to BMP‐7, and this was reduced by ∼70% by RA. This inhibitory effect of RA was mediated primarily by retinoic acid receptors (RARs) and it exhibited substantial specificity because it was not associated with changes in either axonal elongation or cell survival. Moreover, mRNAs for enzymes required for synthesis of RA were expressed in the sympathetic neurons and retinoid activity was released from superior cervical ganglia. These observations suggest that retinoids may function as endogenous morphogens and regulate neural cell shape and polarity in developing sympathetic ganglia. © 2000 John Wiley & Sons, Inc. J Neurobiol 42: 383–393, 2000

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Bone morphogenetic protein-2 and retinoic acid induce neurotrophin-3 responsiveness in developing rat sympathetic neurons

Cited by 39 publications

References 35 publications

Regulation of Glial Cell Line-Derived Neurotrophic Factor Responsiveness in Developing Rat Sympathetic Neurons by Retinoic Acid and Bone Morphogenetic Protein-2

Regulation of Glial Cell Line-Derived Neurotrophic Factor Responsiveness in Developing Rat Sympathetic Neurons by Retinoic Acid and Bone Morphogenetic Protein-2

Target-derived BMP signaling limits sensory neuron number and the extent of peripheral innervation in vivo

Retinoic acid regulates the morphological development of sympathetic neurons

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