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PMID:16314491

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Citation

Ma, L, Lu, MF, Schwartz, RJ and Martin, JF (2005) Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development 132:5601-11

Abstract

Cardiac cushion development provides a valuable system to investigate epithelial to mesenchymal transition (EMT), a fundamental process in development and tumor progression. In the atrioventricular (AV) canal, endocardial cells lining the heart respond to a myocardial-derived signal, undergo EMT, and contribute to cushion mesenchyme. Here, we inactivated bone morphogenetic protein 2 (Bmp2) in the AV myocardium of mice. We show that Bmp2 has three functions in the AV canal: to enhance formation of the cardiac jelly, to induce endocardial EMT and to pattern the AV myocardium. Bmp2 is required for myocardial expression of Has2, a crucial component of the cardiac jelly matrix. During EMT, Bmp2 promotes expression of the basic helix-loop-helix factor Twist1, previously implicated in EMT in cancer metastases, and the homeobox genes Msx1 and Msx2. Deletion of the Bmp type 1A receptor, Bmpr1a, in endocardium also resulted in failed cushion formation, indicating that Bmp2 signals directly to cushion-forming endocardium to induce EMT. Lastly, we show that Bmp2 mutants failed to specify the AV myocardium with loss of Tbx2 expression uncovering a myocardial, planar signaling function for Bmp2. Our data indicate that Bmp2 has a crucial role in coordinating multiple aspects of AV canal morphogenesis.

Links

PubMed Online version:10.1242/dev.02156

Keywords

Animals; Body Patterning; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein Receptors, Type I/metabolism; Bone Morphogenetic Proteins/genetics; Bone Morphogenetic Proteins/physiology; DNA-Binding Proteins/metabolism; Endocardium/embryology; Endocardium/physiology; Epithelium/embryology; Epithelium/physiology; Glucuronosyltransferase/metabolism; Heart/embryology; Heart/physiology; Homeodomain Proteins/metabolism; MSX1 Transcription Factor/metabolism; Mesoderm/physiology; Mice; Morphogenesis; Mutation; Nuclear Proteins/metabolism; Signal Transduction; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/physiology; Twist Transcription Factor/metabolism

Significance

Annotations

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

MOUSE:BMP2

acts_upstream_of_or_within

GO:0001701: in utero embryonic development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0007507: heart development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

  • results_in_development_of:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0003203: endocardial cushion morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0003181: atrioventricular valve morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0060039: pericardium development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

  • results_in_development_of:(EMAPA:16131)

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0055008: cardiac muscle tissue morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

  • regulates_o_occurs_in:(EMAPA:16546)
  • has_input:(MGI:MGI:102469)|regulates_o_occurs_in(EMAPA:16546)
  • has_input:(MGI:MGI:98872)|regulates_o_occurs_in(EMAPA:16546)
  • has_input:(MGI:MGI:97168)|regulates_o_occurs_in(EMAPA:16546)
  • has_input:(MGI:MGI:97169)|regulates_o_occurs_in(EMAPA:16546)
  • has_input:(MGI:MGI:1336883)|regulates_o_occurs_in(EMAPA:16546)
  • has_input:(MGI:MGI:97363)|regulates_o_occurs_in(EMAPA:16546)
  • has_input:(MGI:MGI:98330)|regulates_o_occurs_in(EMAPA:16546)
  • has_input:(MGI:MGI:98494)|regulates_o_occurs_in(EMAPA:16546)
  • has_input:(MGI:MGI:107821)

Seeded From UniProt

complete

MOUSE:BMR1A

acts_upstream_of_or_within

GO:0003272: endocardial cushion formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

  • regulates_o_occurs_in:(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:102469)|regulates_o_occurs_in(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:98872)|regulates_o_occurs_in(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:97168)|regulates_o_occurs_in(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:97169)|regulates_o_occurs_in(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:1336883)|regulates_o_occurs_in(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:97363)|regulates_o_occurs_in(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:98330)|regulates_o_occurs_in(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:98494)|regulates_o_occurs_in(EMAPA:16546)
  • has_regulation_target:(MGI:MGI:107821)

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0035054: embryonic heart tube anterior/posterior pattern specification

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

Seeded From UniProt

complete

MOUSE:BMP2

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0001701: in utero embryonic development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

has_participant:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0003181: atrioventricular valve morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

has_participant:(EMAPA:16546)

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0003203: endocardial cushion morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

has_participant:(EMAPA:16696)

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0007219: Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0007507: heart development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

results_in_development_of:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0010718: positive regulation of epithelial to mesenchymal transition

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0055008: cardiac muscle tissue morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

has_participant:(EMAPA:16339)|has_participant:(EMAPA:16819)

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0060039: pericardium development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3583785

P

results_in_development_of:(EMAPA:16131)

Seeded From UniProt

complete

See also

References

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