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PMID:21490958

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Citation

Grice, SJ and Liu, JL (2011) Survival motor neuron protein regulates stem cell division, proliferation, and differentiation in Drosophila. PLoS Genet. 7:e1002030

Abstract

Spinal muscular atrophy is a severe neurogenic disease that is caused by mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein is required for the assembly of small nuclear ribonucleoproteins and a dramatic reduction of the protein leads to cell death. It is currently unknown how the reduction of this ubiquitously essential protein can lead to tissue-specific abnormalities. In addition, it is still not known whether the disease is caused by developmental or degenerative defects. Using the Drosophila system, we show that SMN is enriched in postembryonic neuroblasts and forms a concentration gradient in the differentiating progeny. In addition to the developing Drosophila larval CNS, Drosophila larval and adult testes have a striking SMN gradient. When SMN is reduced in postembryonic neuroblasts using MARCM clonal analysis, cell proliferation and clone formation defects occur. These SMN mutant neuroblasts fail to correctly localise Miranda and have reduced levels of snRNAs. When SMN is removed, germline stem cells are lost more frequently. We also show that changes in SMN levels can disrupt the correct timing of cell differentiation. We conclude that highly regulated SMN levels are essential to drive timely cell proliferation and cell differentiation.

Links

PubMed PMC3072375 Online version:10.1371/journal.pgen.1002030

Keywords

Animals; Cell Cycle Proteins/metabolism; Cell Differentiation/genetics; Cell Proliferation; Central Nervous System/embryology; Central Nervous System/metabolism; Central Nervous System/pathology; Drosophila/cytology; Drosophila/genetics; Drosophila/metabolism; Drosophila Proteins/metabolism; Female; Gene Expression Regulation, Developmental; Male; Mutation/genetics; RNA, Small Nuclear/metabolism; SMN Complex Proteins/genetics; SMN Complex Proteins/metabolism; Stem Cells/cytology; Stem Cells/metabolism; Testis/metabolism

Significance

Annotations

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

DROME:Q9VDR7

located_in

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000031)

Seeded From UniProt

complete

DROME:Q9VDR7

located_in

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:SMN

involved_in

GO:0017145: stem cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000031)
  • occurs_in:(UBERON:0000069)|occurs_in:(CL:0000016)

Seeded From UniProt

complete

DROME:SMN

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000031)|part_of:(UBERON:0000473)

Seeded From UniProt

complete

DROME:SMN

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SMN

involved_in

GO:0048863: stem cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000031)
  • occurs_in:(UBERON:0000069)|occurs_in:(CL:0000016)

Seeded From UniProt

complete

DROME:SMN

involved_in

GO:0072089: stem cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000031)
  • occurs_in:(UBERON:0000069)|occurs_in:(CL:0000016)

Seeded From UniProt

complete

DROME:SMN

involved_in

GO:0045175: basal protein localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000031)
  • has_input:(UniProtKB:Q9VDR7)

Seeded From UniProt

complete

DROME:Q9VV74

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VV74

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000031)|part_of:(UBERON:0000473)

Seeded From UniProt

complete

DROME:Q9VV74

GO:0035209: pupal development

ECO:0000315:

P

Fig 8F.

Using daughterless-GAL4 (da-GAL4) and a functional SMN-YFP transgene: the da-GAL4; SMN-YFP larvae had irregular pupation patterns with many larvae pupated earlier than the da-GAL4 controls.

complete

DROME:Q9VV74

GO:0007419: ventral cord development

ECO:0000315:

P

Fig 8(A-C).

At 3 and 4 days after hatching the ventral nerve cord of the larvae were measured. da-GAL4; SMN-YFP CNS are larger than control at each time point.

complete

DROME:Q9VV74

involved_in

GO:0072089: stem cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000031)
  • occurs_in:(UBERON:0000069)|occurs_in:(CL:0000016)

Seeded From UniProt

complete

DROME:Q9VV74

involved_in

GO:0048863: stem cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000031)
  • occurs_in:(UBERON:0000069)|occurs_in:(CL:0000016)

Seeded From UniProt

complete

DROME:Q9VV74

involved_in

GO:0045175: basal protein localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000031)
  • has_input:(UniProtKB:Q9VDR7)

Seeded From UniProt

complete

DROME:Q9VV74

involved_in

GO:0017145: stem cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000031)
  • occurs_in:(UBERON:0000069)|occurs_in:(CL:0000016)

Seeded From UniProt

complete


See also

References

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