Requirement of adenylate cyclase 1 for the ephrin-A5-dependent retraction of exuberant retinal axons.
The calcium-stimulated adenylate cyclase 1 (AC1) has been shown to be required for the refinement of the retinotopic map, but the mechanisms involved are not known. To investigate this question, we devised a retinotectal coculture preparation that reproduces the gradual acquisition of topographic specificity along the rostrocaudal axis of the superior colliculus (SC). Temporal retinal axons invade the entire SC at 4 d in vitro (DIV) and eliminate exuberant branches caudally by 12 DIV. Temporal and nasal axons form branches preferentially in the rostral or caudal SC, respectively. Retinal explants from AC1-deficient mice, AC1(brl/brl), maintain exuberant branches and lose the regional selectivity of branching when confronted with wild-type (WT) SC. Conversely, WT retinas correctly target AC1(brl/brl) collicular explants. The effects of AC1 loss of function in the retina are mimicked by the blockade of ephrin-A5 signaling in WT cocultures. Video microscopic analyses show that AC1(brl/brl) axons have modified responses to ephrin-A5: the collapse of the growth cones occurs, but the rearward movement of the axon is arrested. Our results demonstrate a presynaptic, cell autonomous role of AC1 in the retina and further indicate that AC1 is necessary to enact a retraction response of the retinal axons to ephrin-A5 during the refinement of the retinotopic map.
Nicol
Xavier
X
Institut National de la Santé et de la Recherche Médicale, U616, University Paris 06, Hôpital Pitié Salpêtrière, Institut Féderatif Neurosciences, F-75013 Paris, France.
Muzerelle
Aude
A
Rio
Jean Paul
JP
Métin
Christine
C
Gaspar
Patricia
P
D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D018920:Coculture Techniques; D036386:Ephrin-A5 / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D012160:Retina / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000254:growth & development*; D014463:Ultrasonography
D036386:Ephrin-A5; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1