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A chemoattractant role for NT-3 in proprioceptive axon guidance.

ABSTRACT: Neurotrophin-3 (NT-3) is required for proprioceptive neuron survival. Deletion of the proapoptotic gene Bax in NT-3 knockout mice rescues these neurons and allows for examination of their axon growth in the absence of NT-3 signaling. TrkC-positive peripheral and central axons from dorsal root ganglia follow proper trajectories and arrive in close proximity to their targets but fail to innervate them. Peripherally, muscle spindles are absent and TrkC-positive axons do not enter their target muscles. Centrally, proprioceptive axons branch in ectopic regions of the spinal cord, even crossing the midline. In vitro assays reveal chemoattractant effects of NT-3 on dorsal root ganglion axons. Our results show that survival factor NT-3 acts as a short-distance axon guidance molecule for muscle sensory afferents as they approach their proper targets.

SUBMITTER: Genc B

PROVIDER: S-EPMC529315 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature

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A chemoattractant role for NT-3 in proprioceptive axon guidance.

Genç Bariş B Ozdinler P Hande PH Mendoza April E AE Erzurumlu Reha S RS

PLoS biology 20041123 12

Neurotrophin-3 (NT-3) is required for proprioceptive neuron survival. Deletion of the proapoptotic gene Bax in NT-3 knockout mice rescues these neurons and allows for examination of their axon growth in the absence of NT-3 signaling. TrkC-positive peripheral and central axons from dorsal root ganglia follow proper trajectories and arrive in close proximity to their targets but fail to innervate them. Peripherally, muscle spindles are absent and TrkC-positive axons do not enter their target muscl ...[more]

PMID: 15550985

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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

A chemoattractant role for NT-3 in proprioceptive axon guidance.

Publications

A chemoattractant role for NT-3 in proprioceptive axon guidance.

Similar Datasets

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