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PMID:10500184

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Citation

Tsukui, T, Capdevila, J, Tamura, K, Ruiz-Lozano, P, Rodriguez-Esteban, C, Yonei-Tamura, S, Magallón, J, Chandraratna, RA, Chien, K, Blumberg, B, Evans, RM and Belmonte, JC (1999) Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1. Proc. Natl. Acad. Sci. U.S.A. 96:11376-81

Abstract

Asymmetric expression of Sonic hedgehog (Shh) in Hensen's node of the chicken embryo plays a key role in the genetic cascade that controls left-right asymmetry, but its involvement in left-right specification in other vertebrates remains unclear. We show that mouse embryos lacking Shh display a variety of laterality defects, including pulmonary left isomerism, alterations of heart looping, and randomization of axial turning. Expression of the left-specific gene Lefty-1 is absent in Shh(-/-) embryos, suggesting that the observed laterality defects could be the result of the lack of Lefty-1. We also demonstrate that retinoic acid (RA) controls Lefty-1 expression in a pathway downstream or parallel to Shh. Further, we provide evidence that RA controls left-right development across vertebrate species. Thus, the roles of Shh and RA in left-right specification indeed are conserved among vertebrates, and the Shh and RA pathways converge in the control of Lefty-1.

Links

PubMed PMC18041

Keywords

Animals; Base Sequence; Chick Embryo; Congenital Abnormalities/etiology; Gene Expression Regulation, Developmental; Hedgehog Proteins; Left-Right Determination Factors; Mice; Mice, Knockout; Molecular Sequence Data; Proteins/physiology; RNA, Messenger/analysis; Trans-Activators; Transforming Growth Factor beta/genetics; Tretinoin/physiology

Significance

Annotations

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

MOUSE:SHH

acts_upstream_of_or_within

GO:0001947: heart looping

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0007507: heart development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

  • results_in_development_of:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060459: left lung development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

  • results_in_development_of:(EMAPA:17653)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060458: right lung development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

  • results_in_development_of:(EMAPA:17661)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060441: epithelial tube branching involved in lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

  • occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060425: lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

Seeded From UniProt

complete

MOUSE:LFTY1

acts_upstream_of_or_within

GO:0032526: response to retinoic acid

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

XENLA:PITX2

involved_in

GO:0003007: heart morphogenesis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

XENLA:PITX2

involved_in

GO:0048562: embryonic organ morphogenesis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

CHICK:AL1A2

involved_in

GO:0001947: heart looping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:AL1A2

involved_in

GO:0003007: heart morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:AL1A2

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:INHBB

involved_in

GO:1900164: nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

CHICK:PITX2

involved_in

GO:0003007: heart morphogenesis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

CHICK:PITX2

involved_in

GO:0048562: embryonic organ morphogenesis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

CHICK:PITX2

involved_in

GO:0003007: heart morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:PITX2

involved_in

GO:0001947: heart looping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:PITX2

involved_in

GO:0032526: response to retinoic acid

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:SHH

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

CHICK:SHH

involved_in

GO:0023052: signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q8QGA0

involved_in

GO:1900164: nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q8QGA0

involved_in

GO:0032526: response to retinoic acid

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060441: epithelial tube branching involved in lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060425: lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

has_participant:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060458: right lung development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

results_in_development_of:(EMAPA:17661)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0060459: left lung development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

results_in_development_of:(EMAPA:17653)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0007507: heart development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

results_in_development_of:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0007368: determination of left/right symmetry

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0001947: heart looping

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857796

P

has_participant:(EMAPA:16105)

Seeded From UniProt

complete


See also

References

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