Polarized Dock Activity Drives Shh-Mediated Axon Guidance.
Open accessAbstract
In the developing spinal cord, Sonic hedgehog (Shh) attracts commissural axons toward the floorplate. How Shh regulates the cytoskeletal remodeling that underlies growth cone turning is unknown. We found that Shh-mediated growth cone turning requires the activity of Docks, which are unconventional GEFs. Knockdown of Dock3 and 4, or their binding partner ELMO1 and 2, abolished commissural axon attraction by Shh in vitro. Dock3/4 and ELMO1/2 were also required for correct commissural axon guidance in vivo. Polarized Dock activity was sufficient to induce axon turning, indicating that Docks are instructive for axon guidance. Mechanistically, we show that Dock and ELMO interact with Boc, the Shh receptor, and that this interaction is reduced upon Shh stimulation. Furthermore, Shh stimulation translocates ELMO to the growth cone periphery and activates Rac1. This identifies Dock/ELMO as an effector complex of non-canonical Shh signaling and demonstrates the instructive role of GEFs in axon guidance.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Dock4 is important for neuronal development and social behaviors.
“Dock4 is important for neuronal development and social behaviors.”
From Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development (2020) · cites this paper as Makihara et al., 2018
Dock4 plays critical roles in axon guidance, dendritic development, and dendritic spine formation, but these results were obtained from in vitro preparations.
“Dock4 has been found to plays critical roles in axon guidance, dendritic development, and dendritic spine formation, but these results were obtained from in vitro preparations 27, 29–31.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [31]
Cited by
Sorted by citations
Guo, D., Peng, Y., Wang, L., Sun, X., Wang, X., Liang, C., Yang, X., Li, S., Xu, J., Ye, W.-C., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-019-0472-7 · Cited by 102 · see citing works
Huang, M., Liang, C., Li, S., Zhang, J., Guo, D., Zhao, B., Liu, Y., Peng, Y., Xu, J., Liu, W., et al. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00577 · Cited by 41 · see citing works
“Moreover, Dock4 is suggested to play important roles in neuronal development such as axon guidance, dendrite development and dendritic spine morphogenesis (Ueda et al., 2008, 2013; Xiao et al., 2013; Makihara et al., 2018).”
Background
- Authors
- Makihara, S., Morin, S., Ferent, J., Côté, J.-F., Yam, P. T., & Charron, F.
- Affiliations
- Montreal Clinical Research Institute (CA)
- Corresponding author
- Yam, Patricia T.
- Charron, Frédéric
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 46
- Issue
- 4
- Pages
- 410-425.e7
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2885792211
- Cited by
- 37
- References
- 0
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 6 · 2022: 9 · 2021: 3 · 2020: 7 · 2019: 5
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Keidanren Ishizaka Memorial Foundation
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec-Santé
- Canada Foundation for Innovation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Sonic hedgehog signaling, axon guidance, commissural axons, floor plate, growth cone turning, ELMo, Rac1, cytoskeletal remodeling, spinal cord development
- MeSH terms
- Axon Guidance, Animals, Axons, Carrier Proteins, Cells, Cultured, Cytoskeletal Proteins, Embryo, Mammalian, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Spinal Cord, Gene Expression Regulation, Developmental, Growth Cones, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, Adaptor Proteins, Signal Transducing, Hedgehog Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
