GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20223754

From GONUTS
Jump to: navigation, search
Citation

Yates, LL, Schnatwinkel, C, Murdoch, JN, Bogani, D, Formstone, CJ, Townsend, S, Greenfield, A, Niswander, LA and Dean, CH (2010) The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis. Hum. Mol. Genet. 19:2251-67

Abstract

The lungs are generated by branching morphogenesis as a result of reciprocal signalling interactions between the epithelium and mesenchyme during development. Mutations that disrupt formation of either the correct number or shape of epithelial branches affect lung function. This, in turn, can lead to congenital abnormalities such as cystadenomatoid malformations, pulmonary hypertension or lung hypoplasia. Defects in lung architecture are also associated with adult lung disease, particularly in cases of idiopathic lung fibrosis. Identifying the signalling pathways which drive epithelial tube formation will likely shed light on both congenital and adult lung disease. Here we show that mutations in the planar cell polarity (PCP) genes Celsr1 and Vangl2 lead to disrupted lung development and defects in lung architecture. Lungs from Celsr1(Crsh) and Vangl2(Lp) mouse mutants are small and misshapen with fewer branches, and by late gestation exhibit thickened interstitial mesenchyme and defective saccular formation. We observe a recapitulation of these branching defects following inhibition of Rho kinase, an important downstream effector of the PCP signalling pathway. Moreover, epithelial integrity is disrupted, cytoskeletal remodelling perturbed and mutant endoderm does not branch normally in response to the chemoattractant FGF10. We further show that Celsr1 and Vangl2 proteins are present in restricted spatial domains within lung epithelium. Our data show that the PCP genes Celsr1 and Vangl2 are required for foetal lung development thereby revealing a novel signalling pathway critical for this process that will enhance our understanding of congenital and adult lung diseases and may in future lead to novel therapeutic strategies.

Links

PubMed PMC2865378 Online version:10.1093/hmg/ddq104

Keywords

Animals; Cell Polarity/genetics; Cell Polarity/physiology; Immunoblotting; Immunohistochemistry; Lung/embryology; Mice; Models, Biological; Morphogenesis/genetics; Morphogenesis/physiology; Mutation/genetics; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/physiology; Oligonucleotides/genetics; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/metabolism; Receptors, G-Protein-Coupled/physiology; Respiratory Mucosa/embryology; Respiratory Mucosa/metabolism; Signal Transduction/genetics

Significance

Annotations

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

MOUSE:CELR1

acts_upstream_of_or_within

GO:0032956: regulation of actin cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

  • regulates_o_occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0007266: Rho protein signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

  • occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0060490: lateral sprouting involved in lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

  • occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0060489: planar dichotomous subdivision of terminal units involved in lung branching morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0060488: orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0032956: regulation of actin cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857642

P

  • regulates_o_occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0007266: Rho protein signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857642

P

  • occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0060490: lateral sprouting involved in lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857642

P

  • occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0060489: planar dichotomous subdivision of terminal units involved in lung branching morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857642

P

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0060488: orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857642

P

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0007266: Rho protein signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0032956: regulation of actin cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

regulates_o_occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0060490: lateral sprouting involved in lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

occurs_in:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0060489: planar dichotomous subdivision of terminal units involved in lung branching morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

has_participant:(EMAPA:16728)

Seeded From UniProt

complete

MOUSE:CELR1

acts_upstream_of_or_within

GO:0060488: orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2668337

P

has_participant:(EMAPA:16728)

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.