The WAVE regulatory complex interacts with Boc and is required for Shh-mediated axon guidance
During development, Shh attracts axons of spinal cord commissural neurons to the floor plate. Shh-mediated attraction of commissural axons requires the receptor Boc. How Boc regulates cytoskeletal changes in growth cones in response to Shh is not fully understood. To identify effectors of Boc in Shh-mediated axon guidance, we used BioID to screen for proteins in proximity to Boc. Top hits included members of the WAVE regulatory complex (WRC), which acts downstream of Rac1 to promote actin cytoskeleton assembly. Therefore, we hypothesized that the WRC is important for Shh-mediated growth cone turning. Using biochemical and cellular assays, we found that Boc directly interacts with the WRC and that this interaction can occur in live cells. Moreover, we found that knockdown of <i>Nckap1</i> and <i>Cyfip1/2,</i> two subunits of the WRC, in commissural neurons, impairs axon attraction toward a Shh gradient. Our results demonstrate that the WRC is required for Shh-mediated axon attraction.
Authors
- Baoyu Chen (ORCID: https://orcid.org/0000-0002-6366-159X)
- Patricia T. Yam
- Kehinde Sulaimon Ayinde (ORCID: https://orcid.org/0000-0002-4511-2562)
- Jean-François Michaud (ORCID: https://orcid.org/0000-0002-7441-8982)
- Rachelle Sauvé
- Stéphane Angers (ORCID: https://orcid.org/0000-0001-7241-9044)
- Nursen Balekoglu
- Sichun Lin (ORCID: https://orcid.org/0000-0002-7070-5765)
- Daniel A. Kramer (ORCID: https://orcid.org/0000-0002-7159-9562)
- Frédéric Charron (ORCID: https://orcid.org/0000-0003-3483-8672)
- Theresia E. B. Stradal (ORCID: https://orcid.org/0000-0002-0352-9474)
- Anika Steffen (ORCID: https://orcid.org/0000-0002-2933-0543)
- Yijun Liu (ORCID: https://orcid.org/0000-0002-1170-0470)
- Kaiyue Zhang (ORCID: https://orcid.org/0000-0002-9906-9053)
Institutions
- Iowa State University (US)
- University of Toronto (CA)
- Occupational Cancer Research Centre (CA)
- Helmholtz Centre for Infection Research (DE)
- Montreal Clinical Research Institute (CA)
- McGill University (CA)
- Université de Montréal (CA)
Publication Details
- Journal
- iScience
- Published
- 2024-11-05
- DOI
- https://doi.org/10.1016/j.isci.2024.111333
- Citations
- 2
- Primary Topic
- Axon Guidance and Neuronal Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.54
Funders
- Canada Foundation for Innovation
- Canada Research Chairs
- National Institutes of Health
- Canadian Institutes of Health Research