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PMID:10521397

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Citation

Yan, YT, Gritsman, K, Ding, J, Burdine, RD, Corrales, JD, Price, SM, Talbot, WS, Schier, AF and Shen, MM (1999) Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation. Genes Dev. 13:2527-37

Abstract

Specification of the left-right (L-R) axis in the vertebrate embryo requires transfer of positional information from the node to the periphery, resulting in asymmetric gene expression in the lateral plate mesoderm. We show that this activation of L-R lateral asymmetry requires the evolutionarily conserved activity of members of the EGF-CFC family of extracellular factors. Targeted disruption of murine Cryptic results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and pulmonary right isomerism, as well as randomized embryo turning and cardiac looping. Similarly, zebrafish one-eyed pinhead (oep) mutants that have been rescued partially by mRNA injection display heterotaxia, including randomization of heart looping and pancreas location. In both Cryptic and oep mutant embryos, L-R asymmetric expression of Nodal/cyclops, Lefty2/antivin, and Pitx2 does not occur in the lateral plate mesoderm, while in Cryptic mutants Lefty1 expression is absent from the prospective floor plate. Notably, L-R asymmetric expression of Nodal at the lateral edges of the node is still observed in Cryptic mutants, indicating that L-R specification has occurred in the node but not the lateral plate. Combined with the previous finding that oep is required for nodal signaling in zebrafish, we propose that a signaling pathway mediated by Nodal and EGF-CFC activities is essential for transfer of L-R positional information from the node.

Links

PubMed PMC317064

Keywords

Animals; Axis; Body Patterning; Embryonic and Fetal Development; Epidermal Growth Factor/genetics; Epidermal Growth Factor/metabolism; Gene Expression; Gene Targeting; Growth Substances/genetics; Growth Substances/metabolism; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Intercellular Signaling Peptides and Proteins; Mice; Mutagenesis; Transcription Factors/genetics; Transcription Factors/metabolism; Zebrafish; Zebrafish Proteins

Significance

Annotations

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

MOUSE:CFC1

acts_upstream_of_or_within

GO:0001947: heart looping

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0001889: liver development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0007368: determination of left/right symmetry

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0009791: post-embryonic development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0003007: heart morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0060541: respiratory system development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0048546: digestive tract morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0048536: spleen development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0060460: left lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete

MOUSE:CFC1

acts_upstream_of_or_within

GO:0060413: atrial septum morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179530

P

Seeded From UniProt

complete


See also

References

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