Engrailed homeoprotein recruits the adenosine A1 receptor to potentiate ephrin A5 function in retinal growth cones
Abstract
Engrailed 1 and engrailed 2 homeoprotein transcription factors (collectively Engrailed) display graded expression in the chick optic tectum where they participate in retino-tectal patterning. In vitro, extracellular Engrailed guides retinal ganglion cell (RGC) axons and synergises with ephrin A5 to provoke the collapse of temporal growth cones. In vivo disruption of endogenous extracellular Engrailed leads to misrouting of RGC axons. Here we characterise the signalling pathway of extracellular Engrailed. Our results show that Engrailed/ephrin A5 synergy in growth cone collapse involves adenosine A1 receptor activation after Engrailed-dependent ATP synthesis, followed by ATP secretion and hydrolysis to adenosine. This is, to our knowledge, the first evidence for a role of the adenosine A1 receptor in axon guidance. Based on these results, together with higher expression of the adenosine A1 receptor in temporal than nasal growth cones, we propose a computational model that illustrates how the interaction between Engrailed, ephrin A5 and adenosine could increase the precision of the retinal projection map.
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From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Stettler et al., 2012
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Self-citation
- Authors
- Stettler, O., Joshi, R. L., Wizenmann, A., Reingruber, J., Holcman, D., Bouillot, C., Castagner, F., Prochiantz, A., & Moya, K. L.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Tübingen (DE)
- Corresponding author
- Prochiantz, Alain
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2012-01-01
- Volume
- 139
- Issue
- 1
- Pages
- 215-224
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2114191977
- Cited by
- 67
- References
- 47
- Citations by year
- 2024: 2 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 10 · 2014: 9 · 2013: 4 · 2012: 5
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-08-BLAN-0162)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- ephrin-A5, adenosine A1 receptor, axon guidance, growth cone collapse, ATP release, adenosine signaling, optic tectum, chick embryo
- MeSH terms
- Engrailed 2 Protein, Adenosine Triphosphate, Animals, Chick Embryo, Fluorescent Antibody Technique, Microscopy, Fluorescence, Models, Biological, Nerve Tissue Proteins, Retina, Blotting, Western, Signal Transduction, Homeodomain Proteins, Growth Cones, Ephrin-A5, Proteomics, Receptor, Adenosine A1
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