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NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord.

Leggere JC, Saito Y, Darnell RB, Tessier-Lavigne M, Junge HJ, Chen Z - Elife (2016)

Bottom Line: RNA-binding proteins (RBPs) control multiple aspects of post-transcriptional gene regulation and function during various biological processes in the nervous system.We found that the NOVA family of RBPs play a key role in neuronal migration, axon outgrowth, and axon guidance.Together, our results demonstrate that the production of DCC splice variants controlled by NOVA has a crucial function during many stages of commissural neuron development.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States.

ABSTRACT
RNA-binding proteins (RBPs) control multiple aspects of post-transcriptional gene regulation and function during various biological processes in the nervous system. To further reveal the functional significance of RBPs during neural development, we carried out an in vivo RNAi screen in the dorsal spinal cord interneurons, including the commissural neurons. We found that the NOVA family of RBPs play a key role in neuronal migration, axon outgrowth, and axon guidance. Interestingly, Nova mutants display similar defects as the knockout of the Dcc transmembrane receptor. We show here that Nova deficiency disrupts the alternative splicing of Dcc, and that restoring Dcc splicing in Nova knockouts is able to rescue the defects. Together, our results demonstrate that the production of DCC splice variants controlled by NOVA has a crucial function during many stages of commissural neuron development.

No MeSH data available.


Related in: MedlinePlus

Rescue of Nova dKOs by Dcc isoforms in embryos labeled with Atoh1-gfp.(A) Nova dKO was electroporated with gfp, Dcclong, or Dccshort. Only Dcclong expression is able to rescue the axon projection defect. (B) Quantification of ventral axon projection in A. The distance from the dorsal margin of the spinal cord to the ventral most axons is compared to the total height of the spinal cord (1/2 ratio). Data are normalized to WT and are represented as the mean ± SEM (one way ANOVA and Bonferroni post test, *p<0.05, **p<0.001). Also see Figure 1—source data 1 for additional quantification. Scale bar, 50 μm.DOI:http://dx.doi.org/10.7554/eLife.14264.023
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fig8s1: Rescue of Nova dKOs by Dcc isoforms in embryos labeled with Atoh1-gfp.(A) Nova dKO was electroporated with gfp, Dcclong, or Dccshort. Only Dcclong expression is able to rescue the axon projection defect. (B) Quantification of ventral axon projection in A. The distance from the dorsal margin of the spinal cord to the ventral most axons is compared to the total height of the spinal cord (1/2 ratio). Data are normalized to WT and are represented as the mean ± SEM (one way ANOVA and Bonferroni post test, *p<0.05, **p<0.001). Also see Figure 1—source data 1 for additional quantification. Scale bar, 50 μm.DOI:http://dx.doi.org/10.7554/eLife.14264.023

Mentions: Furthermore, using the Atoh1-gfp marker, we also found that Dcclong expression, but not Dccshortexpression was able to rescue the axon projection defect in Nova dKOs to a large extent (Figure 8—figure supplement 1, Figure 1—source data 1).


NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord.

Leggere JC, Saito Y, Darnell RB, Tessier-Lavigne M, Junge HJ, Chen Z - Elife (2016)

Rescue of Nova dKOs by Dcc isoforms in embryos labeled with Atoh1-gfp.(A) Nova dKO was electroporated with gfp, Dcclong, or Dccshort. Only Dcclong expression is able to rescue the axon projection defect. (B) Quantification of ventral axon projection in A. The distance from the dorsal margin of the spinal cord to the ventral most axons is compared to the total height of the spinal cord (1/2 ratio). Data are normalized to WT and are represented as the mean ± SEM (one way ANOVA and Bonferroni post test, *p<0.05, **p<0.001). Also see Figure 1—source data 1 for additional quantification. Scale bar, 50 μm.DOI:http://dx.doi.org/10.7554/eLife.14264.023
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4930329&req=5

fig8s1: Rescue of Nova dKOs by Dcc isoforms in embryos labeled with Atoh1-gfp.(A) Nova dKO was electroporated with gfp, Dcclong, or Dccshort. Only Dcclong expression is able to rescue the axon projection defect. (B) Quantification of ventral axon projection in A. The distance from the dorsal margin of the spinal cord to the ventral most axons is compared to the total height of the spinal cord (1/2 ratio). Data are normalized to WT and are represented as the mean ± SEM (one way ANOVA and Bonferroni post test, *p<0.05, **p<0.001). Also see Figure 1—source data 1 for additional quantification. Scale bar, 50 μm.DOI:http://dx.doi.org/10.7554/eLife.14264.023
Mentions: Furthermore, using the Atoh1-gfp marker, we also found that Dcclong expression, but not Dccshortexpression was able to rescue the axon projection defect in Nova dKOs to a large extent (Figure 8—figure supplement 1, Figure 1—source data 1).

Bottom Line: RNA-binding proteins (RBPs) control multiple aspects of post-transcriptional gene regulation and function during various biological processes in the nervous system.We found that the NOVA family of RBPs play a key role in neuronal migration, axon outgrowth, and axon guidance.Together, our results demonstrate that the production of DCC splice variants controlled by NOVA has a crucial function during many stages of commissural neuron development.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States.

ABSTRACT
RNA-binding proteins (RBPs) control multiple aspects of post-transcriptional gene regulation and function during various biological processes in the nervous system. To further reveal the functional significance of RBPs during neural development, we carried out an in vivo RNAi screen in the dorsal spinal cord interneurons, including the commissural neurons. We found that the NOVA family of RBPs play a key role in neuronal migration, axon outgrowth, and axon guidance. Interestingly, Nova mutants display similar defects as the knockout of the Dcc transmembrane receptor. We show here that Nova deficiency disrupts the alternative splicing of Dcc, and that restoring Dcc splicing in Nova knockouts is able to rescue the defects. Together, our results demonstrate that the production of DCC splice variants controlled by NOVA has a crucial function during many stages of commissural neuron development.

No MeSH data available.


Related in: MedlinePlus