Abstract
We have studied the role of the tumor necrosis factor superfamily member APRIL in the development of embryonic mouse midbrain dopaminergic neurons in vitro and in vivo. In culture, soluble APRIL enhanced axon growth during a window of development between E12 and E14 when nigrostriatal axons are growing to their targets in the striatum in vivo. April transcripts were detected in both the striatum and midbrain during this period and at later stages. The axon growth–enhancing effect of APRIL was similar to that of glial cell-derived neurotrophic factor (GDNF), but in contrast to GDNF, APRIL did not promote the survival of midbrain dopaminergic neurons. The effect of APRIL on axon growth was prevented by function-blocking antibodies to one of its receptors, BCMA (TNFRSF13A), but not by function-blocking antibodies to the other APRIL receptor, TACI (TNFRSF13B), suggesting that the effects of APRIL on axon growth are mediated by BCMA. In vivo, there was a significant reduction in the density of midbrain dopaminergic projections to the striatum in April −/− embryos compared with wild type littermates at E14. These findings demonstrate that APRIL is a physiologically relevant factor for the nigrostriatal projection. Given the importance of the degeneration of dopaminergic nigrostriatal connections in the pathogenesis and progression of Parkinson's disease, our findings contribute to our understanding of the factors that establish nigrostriatal integrity.
| Original language | English |
|---|---|
| Pages (from-to) | 97-103 |
| Number of pages | 7 |
| Journal | Experimental Neurology |
| Volume | 298 |
| Early online date | 11 Sep 2017 |
| DOIs | |
| Publication status | Published - 1 Dec 2017 |
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Keywords
- APRIL knockout mice
- Axon growth
- Midbrain dopaminergic neuron
- Nigrostriatal projection
- TNF superfamily
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TNF superfamily member APRIL enhances midbrain dopaminergic axon growth and contributes to the nigrostriatal projection in vivo. / McWilliams, Thomas G.; Howard, Laura; Wyatt, Sean; Davies, Alun M. (Lead / Corresponding author).
In: Experimental Neurology, Vol. 298, 01.12.2017, p. 97-103.Research output: Contribution to journal › Article
TY - JOUR
T1 - TNF superfamily member APRIL enhances midbrain dopaminergic axon growth and contributes to the nigrostriatal projection in vivo
AU - McWilliams, Thomas G.
AU - Howard, Laura
AU - Wyatt, Sean
AU - Davies, Alun M.
N1 - This work was supported by grants 103852 and 086842 from the Wellcome Trust.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - We have studied the role of the tumor necrosis factor superfamily member APRIL in the development of embryonic mouse midbrain dopaminergic neurons in vitro and in vivo. In culture, soluble APRIL enhanced axon growth during a window of development between E12 and E14 when nigrostriatal axons are growing to their targets in the striatum in vivo. April transcripts were detected in both the striatum and midbrain during this period and at later stages. The axon growth–enhancing effect of APRIL was similar to that of glial cell-derived neurotrophic factor (GDNF), but in contrast to GDNF, APRIL did not promote the survival of midbrain dopaminergic neurons. The effect of APRIL on axon growth was prevented by function-blocking antibodies to one of its receptors, BCMA (TNFRSF13A), but not by function-blocking antibodies to the other APRIL receptor, TACI (TNFRSF13B), suggesting that the effects of APRIL on axon growth are mediated by BCMA. In vivo, there was a significant reduction in the density of midbrain dopaminergic projections to the striatum in April −/− embryos compared with wild type littermates at E14. These findings demonstrate that APRIL is a physiologically relevant factor for the nigrostriatal projection. Given the importance of the degeneration of dopaminergic nigrostriatal connections in the pathogenesis and progression of Parkinson's disease, our findings contribute to our understanding of the factors that establish nigrostriatal integrity.
AB - We have studied the role of the tumor necrosis factor superfamily member APRIL in the development of embryonic mouse midbrain dopaminergic neurons in vitro and in vivo. In culture, soluble APRIL enhanced axon growth during a window of development between E12 and E14 when nigrostriatal axons are growing to their targets in the striatum in vivo. April transcripts were detected in both the striatum and midbrain during this period and at later stages. The axon growth–enhancing effect of APRIL was similar to that of glial cell-derived neurotrophic factor (GDNF), but in contrast to GDNF, APRIL did not promote the survival of midbrain dopaminergic neurons. The effect of APRIL on axon growth was prevented by function-blocking antibodies to one of its receptors, BCMA (TNFRSF13A), but not by function-blocking antibodies to the other APRIL receptor, TACI (TNFRSF13B), suggesting that the effects of APRIL on axon growth are mediated by BCMA. In vivo, there was a significant reduction in the density of midbrain dopaminergic projections to the striatum in April −/− embryos compared with wild type littermates at E14. These findings demonstrate that APRIL is a physiologically relevant factor for the nigrostriatal projection. Given the importance of the degeneration of dopaminergic nigrostriatal connections in the pathogenesis and progression of Parkinson's disease, our findings contribute to our understanding of the factors that establish nigrostriatal integrity.
KW - APRIL knockout mice
KW - Axon growth
KW - Midbrain dopaminergic neuron
KW - Nigrostriatal projection
KW - TNF superfamily
U2 - 10.1016/j.expneurol.2017.09.007
DO - 10.1016/j.expneurol.2017.09.007
M3 - Article
VL - 298
SP - 97
EP - 103
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
ER -