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PMID: 10721990 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling.

Cell ·Vol. 100 ·No. 5 ·2000-03-03 ·Pages 525-35

Hall AC, Lucas FR, Salinas PC

Abstract

Synapse formation requires changes in cell morphology and the upregulation and localization of synaptic proteins. In the cerebellum, mossy fibers undergo extensive remodeling as they contact several granule cells and form complex, multisynaptic glomerular rosettes. Here we show that granule cells secrete factors that induce axon and growth cone remodeling in mossy fibers. This effect is blocked by the WNT antagonist, sFRP-1, and mimicked by WNT-7a, which is expressed by granule cells. WNT-7a also induces synapsin I clustering at remodeled areas of mossy fibers, a preliminary step in synaptogenesis. Wnt-7a mutant mice show a delay in the morphological maturation of glomerular rosettes and in the accumulation of synapsin I. We propose that WNT-7a can function as a synaptogenic factor.

MeSH Terms

Animals Axons/physiology,ultrastructure Biological Factors/metabolism Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors Cell Differentiation Cells, Cultured Cerebellar Cortex/cytology,embryology Coculture Techniques Culture Media, Conditioned Culture Media, Serum-Free/pharmacology Dendrites/physiology,ultrastructure Glycogen Synthase Kinase 3 Glycoproteins Growth Cones/physiology Inositol/pharmacology Intracellular Signaling Peptides and Proteins Lithium/pharmacology Mice Mice, Knockout Microtubule-Associated Proteins/metabolism Nerve Fibers/physiology Nerve Tissue Proteins/physiology Neuronal Plasticity Neurons/metabolism Phosphorylation Protein Processing, Post-Translational Proteins/physiology Proto-Oncogene Proteins/physiology Recombinant Fusion Proteins/physiology Signal Transduction Synapses/physiology Synapsins/metabolism Transfection Wnt Proteins

Chemicals

Biological Factors Culture Media, Conditioned Culture Media, Serum-Free Glycoproteins Intracellular Signaling Peptides and Proteins Microtubule-Associated Proteins Nerve Tissue Proteins Proteins Proto-Oncogene Proteins Recombinant Fusion Proteins Synapsins WD repeat containing planar cell polarity effector Wnt Proteins Wnt7a protein, mouse Inositol Lithium Calcium-Calmodulin-Dependent Protein Kinases Glycogen Synthase Kinase 3

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Hall A C

Developmental Biology Research Centre, The Randall Institute, King's College London, United Kingdom.

Lucas F R

Salinas P C

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)80689-3

Published

2000-03-03

Pages

525-35

Language

English

Region

United States

NLM ID

0413066

Subset

Corrections

CommentIn

PMID: 10721986

External Links

PubMed source DOI: 10.1016/s0092-8674(00)80689-3 View journal details

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Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling.

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