ZFIN ID: ZDB-PUB-100601-16
The Calmodulin-Stimulated Adenylate Cyclase ADCY8 Sets the Sensitivity of Zebrafish Retinal Axons to Midline Repellents and Is Required for Normal Midline Crossing
Xu, H., Leinwand, S.G., Dell, A.L., Fried-Cassorla, E., and Raper, J.A.
Date: 2010
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience   30(21): 7423-7433 (Journal)
Registered Authors: Raper, Jonathan
Keywords: none
MeSH Terms:
  • Adenylyl Cyclases/genetics
  • Adenylyl Cyclases/physiology*
  • Animals
  • Animals, Genetically Modified
  • Axons/drug effects
  • Axons/physiology*
  • Cell Movement/drug effects
  • Cell Movement/genetics
  • Cell Movement/physiology*
  • Cell Transplantation
  • Cells, Cultured
  • Chemokine CXCL12/pharmacology
  • Chick Embryo
  • Colforsin/pharmacology
  • Cyclic AMP/metabolism
  • Electroporation/methods
  • Embryo, Nonmammalian
  • Female
  • Functional Laterality
  • GAP-43 Protein/genetics
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/physiology*
  • Green Fluorescent Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Male
  • Mutation/genetics
  • Nerve Tissue Proteins/metabolism
  • Oligoribonucleotides, Antisense/pharmacology
  • Retina/cytology*
  • Retinal Ganglion Cells/cytology*
  • Retinal Ganglion Cells/drug effects
  • Retinal Ganglion Cells/metabolism
  • Transfection
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 20505109 Full text @ J. Neurosci.
The chemokine SDF1 activates a cAMP-mediated signaling pathway that antagonizes retinal responses to the midline repellent slit. We show that knocking down the calmodulin-activated adenylate cyclase ADCY8 makes retinal axons insensitive to SDF1. Experiments in vivo using male and female zebrafish (Danio rerio) confirm a mutual antagonism between slit signaling and ADCY8-mediated signaling. Unexpectedly, knockdown of ADCY8 or another calmodulin-activated cyclase, ADCY1, induces ipsilateral misprojections of retinal axons that would normally cross the ventral midline. We demonstrate a cell-autonomous requirement for ADCY8 in retinal neurons for normal midline crossing. These findings are the first to show that ADCY8 is required for axonal pathfinding before axons reach their targets. They support a model in which ADCY8 is an essential component of a signaling pathway that opposes repellent signaling. Finally, they demonstrate that ADCY8 helps regulate retinal sensitivity to midline guidance cues.