Abstract
The netrins and slits are two families of widely conserved cues that guide axons and cells along the dorsal-ventral (D-V) axis of animals. These cues typically emanate from the dorsal or ventral midlines and provide spatial information to migrating cells by forming gradients along the D-V axis. Some cell types, however, extend processes to both the dorsal and ventral midlines, suggesting the existence of additional guidance cues that are secreted from both midlines. Here, we report that a previously uncharacterized protein called MADD-4 is secreted by the dorsal and ventral nerve cords of the nematode C. elegans to attract sensory axons and muscle membrane extensions called muscle arms. MADD-4's activity is dependent on UNC-40/DCC, a netrin receptor, which functions cell-autonomously to direct membrane extension. The biological role of MADD-4 orthologs, including ADAMTSL1 and 3 in mammals, is unknown. MADD-4 may therefore represent the founding member of a family of guidance proteins.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ADAMTS Proteins
-
Animals
-
Animals, Genetically Modified
-
Axons / metabolism
-
Caenorhabditis elegans / genetics*
-
Caenorhabditis elegans / growth & development
-
Caenorhabditis elegans / metabolism
-
Caenorhabditis elegans Proteins / genetics*
-
Caenorhabditis elegans Proteins / metabolism
-
Cell Adhesion Molecules / metabolism
-
Cell Movement
-
Cues*
-
Extracellular Matrix Proteins / metabolism
-
Gene Expression Regulation, Developmental
-
Guanine Nucleotide Exchange Factors / genetics
-
Guanine Nucleotide Exchange Factors / metabolism
-
Humans
-
Motor Neurons / cytology
-
Motor Neurons / metabolism*
-
Muscles / cytology
-
Muscles / metabolism
-
Mutation / genetics*
-
Nerve Tissue / cytology
-
Nerve Tissue / metabolism
-
Nerve Tissue Proteins / genetics*
-
Nerve Tissue Proteins / metabolism
-
Netrin Receptors
-
Promoter Regions, Genetic / genetics
-
Receptors, Cell Surface / genetics
-
Receptors, Cell Surface / metabolism
Substances
-
ADAMTSL1 protein, human
-
ADAMTSL3 protein, human
-
Caenorhabditis elegans Proteins
-
Cell Adhesion Molecules
-
Extracellular Matrix Proteins
-
Guanine Nucleotide Exchange Factors
-
MADD-4 protein, C elegans
-
Nerve Tissue Proteins
-
Netrin Receptors
-
Receptors, Cell Surface
-
UNC-40 protein, C elegans
-
ADAMTS Proteins