RGD Reference Report - Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes. - Rat Genome Database

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Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes.

Authors: Yu, Huimin  Ye, Xin  Guo, Nini  Nathans, Jeremy 
Citation: Yu H, etal., Development. 2012 Dec 1;139(23):4383-94. doi: 10.1242/dev.083352. Epub 2012 Oct 24.
RGD ID: 13208951
Pubmed: PMID:23095888   (View Abstract at PubMed)
PMCID: PMC3509732   (View Article at PubMed Central)
DOI: DOI:10.1242/dev.083352   (Journal Full-text)

Frizzled (Fz) 2 and Fz7, together with Fz1, form a distinct subfamily within the Frizzled family of Wnt receptors. Using targeted gene deletion, we show that: Fz7(-/-) mice exhibit tail truncation and kinking with 100% penetrance and ventricular septal defects (VSDs) with ~15% penetrance; Fz2(+/-);Fz7(-/-) mice exhibit VSDs with ~50% penetrance and cleft palate with less than 10% penetrance; and Fz2(-/-);Fz7(-/-) mice exhibit convergent extension defects and mid-gestational lethality with 100% penetrance. When Fz2 and/or Fz7 mutations are combined with mutations in Vangl2, Dvl3, Wnt3a, Wnt5a or Wnt11, an increased frequency of VSDs is observed with Dvl3, Wnt3a and Wnt11; an increased frequency of palate closure defects is observed with Vangl2; and early lethality and enhanced tail shortening are observed with Wnt5a. To assess the signaling pathways that underlie these and other Frizzled-mediated genetic interactions, we used transfected mammalian cells to analyze (1) canonical Wnt signaling induced by all pairwise combinations of the ten mouse Frizzleds and the 19 mouse Wnts and (2) localization of each Frizzled at cell-cell junctional complexes formed by mouse Celsr1, a likely indicator of competence for planar cell polarity signaling. These in vitro experiments indicate that Fz2 and Fz7 are competent to signal via the canonical pathway. Taken together, the data suggest that genetic interactions between Fz2, Fz7 and Vangl2, Dvl3 and Wnt genes reflect interactions among different signaling pathways in developmental processes that are highly sensitive to perturbations in Frizzled signaling.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Wnt signaling pathway  ISOCdk15 (Mus musculus)13208951; 13208951 RGD 
Wnt signaling pathway  IMP 13208951 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cdk15  (cyclin-dependent kinase 15)

Genes (Mus musculus)
Cdk15  (cyclin dependent kinase 15)

Genes (Homo sapiens)
CDK15  (cyclin dependent kinase 15)


Additional Information