Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans.

Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Research Abstract Details 

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Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Abstract Text:

Oxygen deprivation can cause severe defects in human brain development, yet the precise cellular and molecular consequences of varying oxygen levels on nervous system development are unknown. We found that hypoxia caused specific axon pathfinding and neuronal migration defects in C. elegans that result from the stabilization of the transcription factor HIF-1 (hypoxia-inducible factor 1) in neurons and muscle. Stabilization of HIF-1 through removal of the proteasomal HIF-1 degradatory pathway phenocopies the hypoxia-induced neuronal defects. Hypoxia-mediated defects in nervous system development depended on signaling through the insulin-like receptor DAF-2, which serves to control the level of reactive oxygen species that also affects axon pathfinding. Hypoxia exerted its effect on axon pathfinding, at least in part, through HIF-1-dependent regulation of the Eph receptor VAB-1. HIF-1-mediated upregulation of VAB-1 protected embryos from hypoxia-induced lethality, but increased VAB-1 levels elicited aberrant axon pathfinding. Similar genetic pathways may cause aberrant human brain development under hypoxic conditions.

Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Publishing Authors By Initials

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Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Nature neuroscience

VOLUME: 11

Page Numbers: 894-900

Journal Abbreviation: Nat. Neurosci.

ISSN: 1097-6256

DAY: 29

MONTH: 06

YEAR: 2008

Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Information

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LANGUAGE: eng

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AFFILIATION: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University Medical Center, New York, New York 10032, USA.

Country: United States

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MEDLINETA: Nat Neurosci

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