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| Status |
Public on May 31, 2024 |
| Title |
Polarized Dock Activity Drives Shh-Mediated Axon Guidance |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In the developing spinal cord, Sonic hedgehog (Shh) attracts commissural axons toward the floor plate. 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.
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| Overall design |
RNA sequencing was performed on commmissural neurons isolated from embryonic day 13 rat embryos cultured for two days in vitro.
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| Contributor(s) |
Charron F, Makihara S, Morin S, Ferent J, Yam PT |
| Citation(s) |
30078728 |
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| Submission date |
May 29, 2024 |
| Last update date |
May 31, 2024 |
| Contact name |
Frederic Charron |
| E-mail(s) |
[email protected]
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| Organization name |
IRCM
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| Street address |
110 Avenue des Pins Ouest
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| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H2W 1R7 |
| Country |
Canada |
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| Platforms (1) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA1118019 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE268644_ens_allfpkm.csv.gz |
548.2 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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