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PMID:19018662

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Citation

Zhu, B, Pennack, JA, McQuilton, P, Forero, MG, Mizuguchi, K, Sutcliffe, B, Gu, CJ, Fenton, JC and Hidalgo, A (2008) Drosophila neurotrophins reveal a common mechanism for nervous system formation. PLoS Biol. 6:e284

Abstract

Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects. By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1 maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring cell death, and it enables targeting by motor neurons. We show that Spätzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases.

Links

PubMed PMC2586362 Online version:10.1371/journal.pbio.0060284

Keywords

Animals; Axons; Base Sequence; Cell Death; Conserved Sequence; Drosophila/embryology; Drosophila/genetics; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/physiology; Gene Expression; Humans; Locomotion; Nerve Growth Factors/chemistry; Nerve Growth Factors/genetics; Nerve Growth Factors/physiology; Nervous System/embryology; Neurons/metabolism; Neurons/physiology; Sequence Analysis, Protein

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:SPZ2

enables

GO:0008083: growth factor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:SPZ2

involved_in

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ2

involved_in

GO:0007399: nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ2

involved_in

GO:0031637: regulation of neuronal synaptic plasticity in response to neurotrophin

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ2

involved_in

GO:0010941: regulation of cell death

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ2

involved_in

GO:0008045: motor neuron axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ2

involved_in

GO:0021556: central nervous system formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ

enables

GO:0008083: growth factor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:SPZ

involved_in

GO:0008045: motor neuron axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ5

enables

GO:0008083: growth factor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:SPZ5

involved_in

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ5

involved_in

GO:0007399: nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ5

involved_in

GO:0031637: regulation of neuronal synaptic plasticity in response to neurotrophin

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ5

involved_in

GO:0010941: regulation of cell death

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ5

involved_in

GO:0008045: motor neuron axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SPZ5

involved_in

GO:0021556: central nervous system formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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