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PMID: 16421306 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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

Nicol X, Muzerelle A, Rio JP, Métin C, Gaspar P

Abstract

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.

MeSH Terms
Adenylyl Cyclases/biosynthesis,genetics,physiology Animals Axons/enzymology,metabolism,ultrastructure Coculture Techniques Ephrin-A5/antagonists & inhibitors,physiology Female Mice Mice, Knockout Pregnancy Retina/diagnostic imaging,enzymology,growth & development Ultrasonography
Chemicals
Ephrin-A5 Adenylyl Cyclases adenylyl cyclase 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Nicol Xavier
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
Rio Jean Paul
Métin Christine
Gaspar Patricia
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2006-01-18
Pages
862-72
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6675379
Subset
IM
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