GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells

Y.H. Takeo, S.A. Shuster, L. Jiang, M. Hu, D.J. Luginbuhl, T. Rülicke, X. Contreras, S. Hippenmeyer, M.J. Wagner, S. Ganguli, L. Luo, BioRxiv (n.d.).


Preprint | Submitted | English
Author
Takeo, Yukari H.; Shuster, S. Andrew; Jiang, Linnie; Hu, Miley; Luginbuhl, David J.; Rülicke, Thomas; Contreras Paniagua, XimenaIST Austria; Hippenmeyer, SimonIST Austria ; Wagner, Mark J.; Ganguli, Surya; Luo, Liqun
Department
Abstract
The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis.
Publishing Year
Date Published
2020-06-15
Journal Title
bioRxiv
Acknowledgement
We thank M. Mishina for GluD2fl frozen embryos, T.C. Südhof and J.I. Morgan for Cbln1fl mice, L. Anderson for help in generating the MADM alleles, W. Joo for a previously unpublished construct, M. Yuzaki, K. Shen, J. Ding, and members of the Luo lab, including J.M. Kebschull, H. Li, J. Li, T. Li, C.M. McLaughlin, D. Pederick, J. Ren, D.C. Wang and C. Xu for discussions and critiques of the manuscript, and M. Yuzaki for supporting Y.H.T. during the final phase of this project. Y.H.T. was supported by a JSPS fellowship; S.A.S. was supported by a Stanford Graduate Fellowship and an NSF Predoctoral Fellowship; L.J. is supported by a Stanford Graduate Fellowship and an NSF Predoctoral Fellowship; M.J.W. is supported by a Burroughs Wellcome Fund CASI Award. This work was supported by an NIH grant (R01-NS050538) to L.L.; the European Research Council (ERC) under the European Union's Horizon 2020 research and innovations programme (No. 725780 LinPro) to S.H.; and Simons and James S. McDonnell Foundations and an NSF CAREER award to S.G.; L.L. is an HHMI investigator.
IST-REx-ID

Cite this

Takeo YH, Shuster SA, Jiang L, et al. GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. bioRxiv. doi:10.1101/2020.06.14.151258
Takeo, Y. H., Shuster, S. A., Jiang, L., Hu, M., Luginbuhl, D. J., Rülicke, T., … Luo, L. (n.d.). GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. BioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.06.14.151258
Takeo, Yukari H., S. Andrew Shuster, Linnie Jiang, Miley Hu, David J. Luginbuhl, Thomas Rülicke, Ximena Contreras, et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.06.14.151258.
Y. H. Takeo et al., “GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells,” bioRxiv. Cold Spring Harbor Laboratory.
Takeo YH, Shuster SA, Jiang L, Hu M, Luginbuhl DJ, Rülicke T, Contreras X, Hippenmeyer S, Wagner MJ, Ganguli S, Luo L. GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. bioRxiv.
Takeo, Yukari H., et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.06.14.151258.
All files available under the following license(s):
Copyright Statement:
This Item is protected by copyright and/or related rights. [...]

Link(s) to Main File(s)
Access Level
OA Open Access

Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar