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PMID:20016102

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Citation

Grimsley-Myers, CM, Sipe, CW, Géléoc, GS and Lu, X (2009) The small GTPase Rac1 regulates auditory hair cell morphogenesis. J. Neurosci. 29:15859-69

Abstract

Morphogenesis of sensory hair cells, in particular their mechanotransduction organelle, the stereociliary bundle, requires highly organized remodeling of the actin cytoskeleton. The roles of Rho family small GTPases during this process remain unknown. Here we show that deletion of Rac1 in the otic epithelium resulted in severe defects in cochlear epithelial morphogenesis. The mutant cochlea was severely shortened with a reduced number of auditory hair cells and cellular organization of the auditory sensory epithelium was abnormal. Rac1 mutant hair cells also displayed defects in planar cell polarity and morphogenesis of the stereociliary bundle, including bundle fragmentation or deformation, and mispositioning or absence of the kinocilium. We further demonstrate that a Rac-PAK (p21-activated kinase) signaling pathway mediates kinocilium-stereocilia interactions and is required for cohesion of the stereociliary bundle. Together, these results reveal a critical function of Rac1 in morphogenesis of the auditory sensory epithelium and stereociliary bundle.

Links

PubMed PMC2847287 Online version:10.1523/JNEUROSCI.3998-09.2009

Keywords

Animals; Animals, Newborn; Cells, Cultured; Epithelial Cells/cytology; Epithelial Cells/physiology; Female; Hair Cells, Auditory/enzymology; Hair Cells, Auditory/physiology; Mice; Mice, Knockout; Morphogenesis/genetics; Morphogenesis/physiology; Neuropeptides/deficiency; Neuropeptides/genetics; Neuropeptides/physiology; Organ of Corti/cytology; Organ of Corti/growth & development; Organ of Corti/physiology; Pregnancy; rac GTP-Binding Proteins/deficiency; rac GTP-Binding Proteins/genetics; rac GTP-Binding Proteins/physiology

Significance

Annotations

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

MOUSE:SPTA1

located_in

GO:0032437: cuticular plate

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CADH1

located_in

GO:0016323: basolateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:CDN1B

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RAC1

acts_upstream_of_or_within

GO:0002093: auditory receptor cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663662
MGI:MGI:2663669

P

  • results_in_morphogenesis_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:RAC1

acts_upstream_of_or_within

GO:0003382: epithelial cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663662
MGI:MGI:2663669

P

  • results_in_morphogenesis_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:RAC1

acts_upstream_of_or_within

GO:0048532: anatomical structure arrangement

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663662
MGI:MGI:2663669

P

  • occurs_in:(EMAPA:19151)

Seeded From UniProt

complete

MOUSE:MYO7A

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:MYO7A

located_in

GO:0032420: stereocilium

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:CTNB1

located_in

GO:0016323: basolateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:FZD3

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:FZD3

located_in

GO:0016324: apical plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:MYO6

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:WHRN

located_in

GO:0032421: stereocilium bundle

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:USH1C

located_in

GO:0032420: stereocilium

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:ESPN

located_in

GO:0032421: stereocilium bundle

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:MYO15

located_in

GO:0032420: stereocilium

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:MYO15

located_in

GO:0032421: stereocilium bundle

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:FZD3

part_of

GO:0016324: apical plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:FZD3

part_of

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:ESPN

part_of

GO:0032421: stereocilium bundle

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:CADH1

part_of

GO:0016323: basolateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:WHRN

part_of

GO:0032421: stereocilium bundle

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:CTNB1

part_of

GO:0016323: basolateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:RAC1

acts_upstream_of_or_within

GO:0045216: cell-cell junction organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663662
MGI:MGI:2663669

P

Seeded From UniProt

complete

MOUSE:RAC1

acts_upstream_of_or_within

GO:0003382: epithelial cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663662
MGI:MGI:2663669

P

results_in_morphogenesis_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:RAC1

acts_upstream_of_or_within

GO:0002093: auditory receptor cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663662
MGI:MGI:2663669

P

results_in_morphogenesis_of:(CL:0000589)

Seeded From UniProt

complete

MOUSE:RAC1

acts_upstream_of_or_within

GO:0048532: anatomical structure arrangement

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663662
MGI:MGI:2663669

P

occurs_in:(EMAPA:19151)

Seeded From UniProt

complete

MOUSE:RAC1

acts_upstream_of_or_within

GO:0090103: cochlea morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663662
MGI:MGI:2663669

P

Seeded From UniProt

complete

MOUSE:CDN1B

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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