Requirement of adenylate cyclase 1 for the ephrin-A5-dependent retraction of exuberant retinal axons

J Neurosci. 2006 Jan 18;26(3):862-72. doi: 10.1523/JNEUROSCI.3385-05.2006.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / biosynthesis
  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / physiology*
  • Animals
  • Axons / enzymology*
  • Axons / metabolism
  • Axons / ultrastructure
  • Coculture Techniques
  • Ephrin-A5 / antagonists & inhibitors
  • Ephrin-A5 / physiology*
  • Female
  • Mice
  • Mice, Knockout
  • Pregnancy
  • Retina / diagnostic imaging
  • Retina / enzymology*
  • Retina / growth & development*
  • Ultrasonography


  • Ephrin-A5
  • Adenylyl Cyclases
  • adenylyl cyclase 1