title: 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.
authors.affiliation: CNRS Unité mixte de Recherche 7241/INSERM U1050, Equipe FRM, Center for Interdisciplinary Research in Biology, Collège de France, 11, place Marcelin Berthelot, 75005 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Stettler
authors.forename: Rajiv L
authors.initials: RL
authors.lastname: Joshi
authors.forename: Andrea
authors.initials: A
authors.lastname: Wizenmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Reingruber
authors.forename: David
authors.initials: D
authors.lastname: Holcman
authors.forename: Colette
authors.initials: C
authors.lastname: Bouillot
authors.forename: François
authors.initials: F
authors.lastname: Castagner
authors.forename: Alain
authors.initials: A
authors.lastname: Prochiantz
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Moya
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002642:Chick Embryo; D036386:Ephrin-A5 / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020439:Growth Cones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D040901:Proteomics; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000099266:Engrailed 2 Protein
chemical_list: D000255:Adenosine Triphosphate; D036386:Ephrin-A5; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D043682:Receptor, Adenosine A1; D000099266:Engrailed 2 Protein; C080330:En1 protein, mouse