Dataset Information

Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126).

ABSTRACT: 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.

SUBMITTER: Schmitz C

PROVIDER: S-EPMC1783400 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126).

Schmitz Caroline C Kinge Parag P Hutter Harald H

Proceedings of the National Academy of Sciences of the United States of America 20070109 3

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 phenot ...[more]

PMID: 17213328

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Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Keywords: Mutant Analysis

Dataset Information

Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126).

Publications

Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126).

Similar Datasets

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