Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126).
The navigation of axons toward their targets is a highly dynamic and precisely regulated process during nervous system development. The molecular basis of this navigation process is only partly understood. In Caenorhabditis elegans, we isolated the RNAi-hypersensitive strain nre-1(hd20) lin-15b(hd126), which allows us to phenocopy axon guidance defects of known genes by feeding RNAi. We used this mutant strain to systematically screen 4,577 genes on chromosomes I and III for axon guidance phenotypes. We identified 93 genes whose down-regulation led to penetrant ventral cord fasciculation defects or motoneuron commissure outgrowth defects. These genes encode various classes of proteins, ranging from secreted or putative cell surface proteins to transcription factors controlling gene expression. A majority of the genes is evolutionary conserved and previously uncharacterized. In addition, we found axon guidance functions for known genes like pry-1, a component of the Wnt-signaling pathway, and ced-1, a receptor required for the engulfment of neurons undergoing apoptosis during development. Our screen provides insights into molecular pathways operating during the generation of neuronal circuits and provides a basis for a more detailed analysis of gene networks regulating axon navigation.
Schmitz
Caroline
C
Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
Kinge
Parag
P
Hutter
Harald
H
D000818:Animals; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000145:classification / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C117260:Pry-1 protein, C elegans; C113701:Unc-1 protein, C elegans; C422043:ced-1 protein, C elegans